Treatment guidelines: Acute Exacerbation of COPD

Chronic obstructive pulmonary disease (COPD) refers to a group of disorders characterized by chronic airflow obstruction/limitation. The airway obstruction is persistent and largely irreversible. It includes two distinct pathophysiological processes - chronic bronchitis and emphysema. Acute exacerbations of these disorders occur during the natural history of progression of this disease. Exacerbations are frequent, more so during winter, resulting in progressive loss of the functional capacity of the lungs leading to progressive dyspnea.

The Ministry of Health and Family Welfare has issued the critical care Guidelines for Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Following are the major recommendations:

Case definition:

There are many definitions for what represents an acute exacerbation of COPD. One of the most widely used definitions evaluates the severity of exacerbation based on three symptoms:

• worsening dyspnea


• increase in sputum purulence


• an increase in sputum volume

Type I exacerbation (severe) have all three symptoms and Type 2 exacerbations (moderate) exhibit two of three symptoms. Type 3 exacerbation (mild) include one of the symptoms and at least one of the following: upper respiratory tract infection within the past 5 days,fever without apparent cause, increased wheezing, increased cough, or a 20% increase in respiratory rate or heart rate over baseline.

Incidence of the Condition in our Country

COPD is currently the fourth leading cause of death worldwide behind cardiovascular disease,cancer and cerebrovascular diseases. The Global Burden of Disease Study estimated that in 1990, the worldwide prevalence of COPD was 9.34 per 1000 men and 7.33 per 1000 women. Depending on the severity of the disease, the 5-year mortality rate for patients with COPD varies from 40%to 70%. The three major causes of death have been identified as COPD itself, lung cancer and cardiovascular disease. The prevalence rates of COPD in males varied from 2.12% to 9.4% in studies conducted in north India and from 1.4% to 4.08% in south India. The respective ranges for females were 1.33%– 4.9% in north India and 2.55%– 2.7% in south India. A majority of cases with chronic COPD (57.4%) were found to suffer from a mild form and only 16% had severe COPD. A large-scale study in Hyderabad city and its surrounding municipalities, covering a population of more than 54 lakh and 28 hospitals/health posts, was done in 2001 to collect cause-specific morbidity data. The rates of hospital admissions of cases with COPD showed an age differential. While the rate was 47.84/100,000 persons at the community level, it was 57.28 for those 18–64 years of age and 546.17 for those above 65 years of age. Treatment cost of a patient with COPD per year (in Rs)· according to Guidelines is Rs 2126 for moderate to severe disease and Rs 10,538 for acute exacerbation.

Differential Diagnosis

Acute exacerbation of COPD should be differentiated from the following disorders

• Congestive cardiac failure


• Bronchial asthma


• Bronchiectasis


• Interstitial lung disease


• Chronic thromboembolic pulmonary disease


• Obesity induced dyspnea


• Chronic destructive lung disease due to old tuberculosis


• Occupational lung disease

Prevention and Counselling

Avoidance of smoking is the single most important factor in prevention of exacerbation of COPD. Yearly influenza vaccine and 5 yearly Pneumococcal vaccine has also been found to be helpful. Education regarding starting early antibiotics with evidence of exacerbation. Avoidance of pollution is advisable Early consultation with physician should be strongly encouraged and patient should be educated about the warning signs of acute exacerbation.

Optimal Diagnostic Criteria, Investigations, Treatment and Referral Criteria

At Secondary Hospital

Clinical Diagnosis:

Patient usually presents with a history of chronic cough and exertional breathlessness with recent increase in cough,breathlessness, increased volume and purulence of sputum. There are usually associated constitutional symptoms like fever, malaise and lack of appetite. Patient may be orthopneic and have swelling of feet, On examination there is increase in respiratory rate, tachycardia, flapping tremor and drowsiness ( if retention of carbon dioxide) . Some patients who have predominant chronic bronchitis show features of chronic corpulmonale (Blue Bloaters) like pedal edema, raised jugular venous pressure, puffy face, central cyanosis, loud pulmonary heart sound and parasternal heave due to right ventricular hypertrophy. On the other patient with predominant emphysema (Pink Puffers) are usually thin built, plethoric due to associated secondary polycythemia, disproportionately dyspneic, features of hyper-inflated lungs like obliteration of liver and cardiac dullness, silent chest.

Investigations:

• Chest Xray – To rule out Pneumothorax. Look for consolidation, pleural effusion,cardiomegaly and features of lung hyperinflation.Look for features of past tuberculosis


• Pulse Oximetry


• Sputum for gram stain, Culture and sensitivity, Acid Fast Bacilli stain.


• Hemogram, blood urea, serum creatinine, serum electrolytes


• Electrocardiogram

Treatment:

1. Oxygen therapy: Controlled humidified oxygen therapy with a Venturi mask (fixed performance device) or low oxygen flow (1-2 litres) with nasal cannula or simple face mask (variable performance device) to keep Spo2 90-92%. Higher oxygen saturation and high concentration of inspired oxygen should be avoided.

Bronchodilators:

• Nebulised beta 2 adrenergic receptor agonists (salbutamol) in patients who are very dyspneic – 2.5-5 mg nebulised every 4-6 hours and as necessary. Watch for tachycardia or arrhythmias


• Inhaled beta 2 adrenergic receptor agonists in patients who are able to take metered dose inhalers (180 mcg) every 2-4 hours


• Nebulised anticholinergic agent (ipratropium bromide) 0.5 mg every 4-6 hrs


• Inhaled Ipratropium bromide 18-36 mcg every 2-4 hours

2. Corticosteroids: Five to 10 days of oral or intravenous corticosteroids is advocated in most cases. Prednisolone 40-60 mg orally or methylprednisolone 60-120 mg intravenously may be used. Appropriate stress ulcer prophylaxis with Ranitidine or Proton Pump inhibitors should be started. Inhaled corticosteroids may be added later when patient has stabilized.

3. Antibiotics: The most common organisms identified in acute exacerbation are Streptococcus pneumonia, moraxellacatarrhalis and hemophilus influenza.In patients with more severe and recurrent disease gram negative organisms like Klebsiella pneumonia and Pseudomonas aeruginosa should also be considered. Initial antibiotic choice is empirical. Usually a macrolide antibiotic like azithromycin or clarithromycin or a quinolone like levofloxacin or moxifloxacin is given. Broader spectrum antibiotics are used for severe disease.

4. Methylxanthines like aminophylline. Though commonly used in India but given the frequent and severe side effect profile,narrow therapeutic window and lack of evidence demonstrating improved outcomes routine use of these agents is not recommended

5. There is no role of mucolytic or chest physiotherapy commonly used practices in acute exacerbation of COPD.

Referral criteria:

Following category of patient should be referred to higher centre.

• Patient who will benefit from non invasive ventilation and if this facility is not available in the primary centre


• Patients in need for intubation and mechanical ventilation


• Patient with hemodynamic instability


• Patient not responding to maximal medical treatment


• Patient with acute exacerbation complicated by associated pneumonia,pneumothorax.


• Patient in whom diagnosis is uncertain and needs further investigation.

At Super Specialty Hospital

Clinical Diagnosis:

Patient usually presents with a history of chronic cough and exertional breathlessness with recent increase in cough,breathlessness, increased volume and purulence of sputum. There are usually associated constitutional symptoms like fever, malaise and lack of appetite. Patient may be orthopneic and have swelling of feet, On examination there is increase in respiratory rate, tachycardia, flapping tremor and drowsiness ( if retention of carbon dioxide) . Some patients who have predominant chronic bronchitis show features of chronic corpulmonale (Blue Bloaters) like pedal edema, raised jugular venous pressure, puffy face, central cyanosis, loud pulmonary heart sound and parasternal heave due to right ventricular hypertrophy. On the other patient with predominant emphysema (Pink Puffers) are usually thin built, plethoric due to associated secondary polycythemia, disproportionately dyspneic, features of hyper-inflated lungs like obliteration of liver and cardiac dullness, silent chest.

Investigations:

• Arterial Blood gas analysis – look for hypercarbia and respiratory acidosis


• Echocardiogram- Low ejection fraction


• D DIMER, Pro BNP – bio markers for venous thromboembolism and congestive cardiac failure respectively


• CT scan of Chest – look for other pulmonary disease, pulmonary thrombus


• Venous Doppler of legs- to rule out deep venous thrombosis

Treatment:

• Non invasive ventilation should be applied simultaneously to a patient in acute respiratory failure in addition to the rest of the treatment based on the clinical criteria, provided there is no contraindication

Non-invasive Positive Pressure Ventilation (NIPPV) is indicated in patients with appropriate diagnosis with potential reversibility and if patient has any two of the following clinical criteria are fulfilled.

• Moderate to severe respiratory distress


• Tachypnea, (RR more than 25 / min)


• Accessory muscle use or abdominal paradox


• Blood gas derangement pH < 7.35, PaCO2 > 45 mm Hg


• PaO2 / FiO2 < 300 or SPO2 < 92% with FiO2 0.5

Contradictions

There are no absolute contraindications for the use of NIPPV. Some contraindications have, however, been suggested

• Non-availability of trained medical personnel


• Inability to protect the airways -Comatose patients, patients with CVA or bulbar involvement, confused and agitated patients. Upper airway obstruction


• Hemodynamic instability- uncontrolled arrhythmia, patient on very high doses of inotropes, recent myocardial infarction.


• Inability to fix the interface -Facial abnormalities, facial burns, facial trauma, facial anomaly.


• Severe GI Symptoms – vomiting, obstructed bowel. Recent GI Surgery., Upper G.I. Bleed


• Life threatening hypoxemia


• Copious secretions


• Conditions where NIPPV has not been found to be effective

Protocol for application of NIPPV For successful noninvasive ventilation.

Patient interface –Nasal or oronasal mask

Mode of ventilation:

• Bi-level positive airway pressure--Spontaneous or spontaneous timed mode in portable pressure ventilators or NIV option on conventional ventilators


• Pressure support /Pressure control /Volume control – conventional ventilators

Ventilator settings

Explain therapy and its benefit to the patient in detail. Also discuss the possibility of intubation.

• Choose the correct size interface. Oronasal mask in acute respiratory failure is preferred.


• Set the NIPPV portable pressure ventilator in spontaneous or spontaneous /timed mode. ,


• Start with very low settings. Start with low inspiratory positive airway pressure (IPAP) of 6 – 8 cm H20 with 2 to 4 cm H20 of EPAP (Expiratory positive airway pressure). The difference between IPAP and EPAP should be at least 4 cm H20.


• Administer oxygen at 2 liters per minute. e) Hold the mask with the hand over his face. Do not fix it.


• Increase EPAP by 1-2 cm increments till all his inspiratory efforts are able to triggers the ventilator.


• If the patient is making inspiratory effort and the ventilator does not respond to that inspiratory effort, it indicates that the patient has not generated enough respiratory effort to counter auto PEEP and trigger the ventilator (in COPD patients). Increase EPAP further till this happens. Most of the patients require EPAP of about 4 to 6 cm H2O.Patient who are obese or have obstructive sleep apnea require higher EPAP.


• When all the patient’s efforts are triggering the ventilator, leave EPAP at that level.


• Now start increasing IPAP in increments of 1-2 cm up to a maximum pressure, which the patient can tolerate without discomfort and there is no major mouth or air leak.


• In some NIPPV machine, inspiratory time (Ti) can be adjusted. Setting the Ti at one second is a reasonable approach. 8


• Now secure interface with head straps. Avoid excessive tightness. If the patient has a nasogastric tube put a seal connector in the dome of the mask to minimize air leakage.


• After titrating the pressure, increase oxygen to bring oxygen saturation to around 90%. m) As the settings may be different in wakefulness and sleep, readjust them accordingly

When NIPPV is being initiated for acute respiratory failure, close monitoring and the capability to initiate endotracheal intubation and other resuscitation measures should be available in the same setup. Start NIPPV preferably in the ICU or in the emergency room in acute respiratory failure.

Application of NIPPV using a Critical Care Ventilator

The first step is to select a ventilator, which is capable of fulfilling the needs of the patient.

• Explain the therapy to the patient


• Choose the appropriate mode. Usually pressure support or pressure control modes are preferred. Standard critical care ventilators using flow by system ( non invasive mode option ) allow the patient to breathe without expending effort to open valves. In selected patients like those suffering from neuromuscular diseases, volume assist or volume control mode may be used.


• Choose an appropriate interface


• Silent ventilator alarms f) Keep FiO2 0.5

Using pressure support/control approach

• Start with low settings like inspiratory pressure support at 5-6 cm H2O and PEEP at 2 cm H2O.


• Initiate NIPPV while holding the mask in place and confirm optimum fit. If it is big or small or loose, change it.


• Hold the mask .do not fix the headgear


• Now increase PEEP till all his inspiratory efforts are able to triggers the ventilator 9


• If the patient is making inspiratory effort and the ventilator does not respond to that inspiratory effort, it indicates that the patient has not generated enough respiratory effort to counter auto PEEP and trigger the ventilator (in COPD patients). Increase PEEP further till this happens.


• Once the patient’s all inspiratory efforts are triggering the ventilator then start increasing pressure support further, keeping certain patient’ comfort in mind. (Reduce respiratory rate, reduced use of accessory muscle etc. Ensure that there are no major leaks.


• When there is significant mouth leak, there may be asynchrony. In that case, pressure control will be the preferred mode of NIPPV and one can set up the inspiratory time to avoid asynchrony.


• After adequate ventilation has been achieved, increase fraction of oxygen concentration to maintain Oxygen saturation more than 90%.


• Secure interface with headgear. It should be tight, but not over-tight. Small leaks are acceptable


• A peak inspiratory pressure more than 25 cm is rarely required in COPD, but higher pressures can be used when using NIPPV for other indications. PEEP is usually titrated between 5-10 cm H2O to improve triggering and oxygenation.

Patient must be monitored very closely clinically. Look for sensorium,dyspnoea, respiratory rate ,respiratory distress, use of accessory muscles, abdominal paradox, Mask comfort and vital signs pulse , blood pressure, ECG monitoring and arterial oxygen saturation, All this must be documented every 15 minutes for the first hour in the clinical notes. Patient will show improvement in parameters if NIPPV is effective. Arterial blood gas sample should be sent after 30mts to 1 hr after the application of NIPPV. In ventilator setting look for air leaks and patient–ventilator interaction.

Monitoring of noninvasive ventilation for acute respiratory failure

Subjective

• Mask comfort 10


• Tolerance of ventilator settings


• Respiratory distress


• Physical findings


• Respiratory rate

Other vital signs

• Accessory muscle use


• Abdominal paradox


• Ventilator parameters


• Air leaking


• Adequacy of pressure support


• Adequacy of PEEP


• Tidal volume (5–7 mL/kg)


• Patient-ventilator synchrony

Gas exchange

• Continuous oximetry (until stable)


• ABGs, baseline and 1–2 hrs, then as indicated

Initially give NIPPV continuously or as long as possible. Once patient is tolerating periods off NIPPV, start discontinuing during day time and give during nighttime. In two to three days patient can be weaned off from the NIPPV.

Intubate and initiate mechanical ventilation in following group of patients

• Those who have failed NIV trial.


• Those who have contraindications of NIV


• Excessive secretions o Hemodynamic instability


• Extreme obesity

Initial Ventilator settings in COPD patient should take into account patients need for prolonged expiration. Appropriate initial ventilator settings would be volume assist control, Tidal volume 8 ml/kg predicted body weight, rate 10-12/min, PEEP of 0-5 cm f H2O , FiO2 titrate for SpO2 90-92 % . High peak flow 70-90 L/min to keep I:E ratio 1:4 or more .

Attempt should not be made to attain normal blood gas but to aim for patient’s baseline values.

Monitor for development of auto PEEP by end expiratory manouever or analyzing ventilator graphics.

Judicious use of sedation and analgesia should be tried

Neuromuscular blockers should be avoided

Deep venous thrombosis prophylaxis, Stress ulcer prophylaxis and nutritional needs should be addressed

Guidelines Developed by -

Rajesh Chawla, Consultant Physician and Intensivist, Indraprastha Apollo Hospital, Delhi