Status Asthmaticus - Harrison's Principles of Internal Medicine (22nd Edition, 2025)

Definition & Context

Pathophysiology of the Acute Attack

• The fundamental abnormality is high resistance to airflow due to airway obstruction (bronchospasm + mucosal edema + mucus plugging).
• Most patients in an attack present with hypocapnia (low PCO2) due to a high respiratory rate driven by dyspnea.
• A normal or near-normal PCO2 in a patient in respiratory distress is an ominous sign - it indicates the patient is tiring and is no longer able to maintain the hyperventilation needed to compensate. This signals impending respiratory failure.

Assessment in the Urgent/Emergency Setting

1. Measure PEFR or FEV1 immediately.
2. Patients with PEFR >60% of predicted frequently respond to beta2-agonists alone.
3. Failure to achieve PEFR >60% or persistent severe tachypnea over 4-6 hours should prompt consideration of hospital admission.

Step-by-Step Management (Harrison's Framework)

Step 1 - Initial (Mild to Moderate)

• Inhaled beta2-agonist up to every 1 hour.
• Consider increasing ICS dose 4- to 5-fold.
• If no adequate control and beta2-agonists needed hourly for several hours → refer for urgent care.

Step 2 - Urgent Care Setting

Step 3 - In-Hospital Management

• Continuous bronchodilator nebulization
• Noninvasive positive-pressure ventilation (NIV/BiPAP) to prevent respiratory exhaustion and avoid intubation
• Helium-oxygen (Heliox) mixtures to decrease the work of breathing
• Antibiotics only if there are signs of infection (not routinely)

Mechanical Ventilation in Status Asthmaticus

• Indication: Respiratory failure, rising PCO2, exhaustion
• Strategy:
  • Low respiratory rates and/or low tidal volumes to decrease peak airway pressures
  • "Permissive hypercapnia" - allow PCO2 to rise deliberately rather than risk barotrauma
  • If critical acidosis develops: temporarily correct with IV sodium bicarbonate to raise pH
  • Neuromuscular paralysis may sometimes be beneficial
  • Bronchoscopy to clear mucus plugs has been described but is potentially dangerous in the context of difficult ventilation

High-Risk Patients (Table 298-6) - Factors Associated with Asthma Mortality

1. History of ICU admission for asthma
2. History of intubation for asthma
3. Illicit drug use
4. Depression
5. New diagnosis within the past year
6. ≥2 emergency department visits in the past 6 months
7. Severe psychosocial problems
8. Lower socioeconomic status
9. On daily prednisone prior to admission

Key Clinical Pearls (Harrison's)

Summary of Drug Choices

Acute Exacerbation of COPD - Harrison's Principles of Internal Medicine (22nd Edition, 2025)

Definition

Epidemiology & Natural History

• Exacerbations are a prominent feature of the natural history of COPD.
• The strongest single predictor of future exacerbation is a history of previous exacerbation.
• Frequency increases as airflow obstruction worsens: patients with FEV1 <50% predicted average 1-3 exacerbations per year.
• Some individuals with severe obstruction still do not exacerbate frequently.
• Additional risk factors: current smoking, elevated pulmonary artery-to-aorta diameter ratio on CT, gastroesophageal reflux.
• COPD exacerbations account for the majority of the $50 billion annual COPD-related healthcare expenditures in the United States.

Precipitating Causes

Patient Assessment

History

• Degree and change in dyspnea (activities of daily living)
• Fever, change in sputum character
• Associated symptoms: wheezing, nausea/vomiting, diarrhea, myalgias, chills
• Prior exacerbation history - previous hospitalization is the single greatest risk factor for re-hospitalization

Physical Examination

• Tachycardia, tachypnea
• Use of accessory muscles
• Perioral or peripheral cyanosis
• Ability to speak in complete sentences
• Mental status (confusion/sleepiness = red flag)
• Chest: focal findings, air movement, wheezing, asymmetry (suggests large airway obstruction or pneumothorax), paradoxical abdominal wall motion

Investigations

Key ABG finding: PCO2 >45 mmHg (hypercarbia) has critical implications for treatment (drives NIV decision).

Criteria for Hospital Admission

1. Respiratory acidosis and hypercarbia (PCO2 >45 mmHg, pH ≤7.35)
2. New or worsening hypoxemia
3. Severe underlying COPD
4. Significant comorbidities (e.g., heart failure)
5. Living situation not conducive to careful observation or delivery of treatment

Treatment of Acute Exacerbations

1. Bronchodilators

• Inhaled beta-agonists + muscarinic antagonists - may be given separately or combined.
• Initially given as nebulized therapy (easier in respiratory distress).
• Conversion to metered-dose inhalers is equally effective when accompanied by education - has economic benefits and eases transition to outpatient care.

2. Antibiotics

• Used in moderate or severe exacerbations for 5-7 days, even without a specific identified pathogen.
• Choice based on local antibiotic susceptibility patterns.
• Common pathogens: S. pneumoniae, H. influenzae, M. catarrhalis, C. pneumoniae.

3. Glucocorticoids

• In hospitalized patients: systemic steroids reduce length of stay, hasten recovery, and reduce risk of subsequent exacerbation/relapse.
• Dose: Oral prednisone 40 mg (or equivalent) for 5 days (current recommendation).
• Most frequent acute complication: hyperglycemia (especially in known diabetics).

4. Supplemental Oxygen

• Target oxygen saturation: 88-92%
• Supplemental O2 does not reduce minute ventilation in patients with hypercarbia.
• It may cause modest increases in arterial PCO2 by altering V/Q relationships - but this should not deter clinicians from correcting hypoxemia.

5. Noninvasive Positive-Pressure Ventilation (NIPPV / NIV)

• Mortality rate
• Need for intubation
• Therapy complications
• Hospital length of stay

• Cardiovascular instability
• Impaired mental status / inability to cooperate
• Copious secretions or inability to clear secretions
• Craniofacial abnormalities or trauma (mask fitting not possible)

6. Invasive Mechanical Ventilation

• Severe respiratory distress
• Hypoxemia
• Severe hypercarbia and/or acidosis despite NIPPV
• Markedly impaired mental status
• Respiratory arrest
• Hemodynamic instability
• Other complications

• Provide sufficient expiratory time (severe airflow obstruction = air trapping)
• Watch for auto-PEEP (intrinsic PEEP) - patients may need to generate significant effort to trigger a breath in demand mode

Prognosis

Post-Exacerbation Management (Preventing Future Exacerbations)

• Triple inhaled therapy (LABA + LAMA + ICS) - reduces mortality in selected patients
• Smoking cessation - improves rate of lung function decline and survival
• Pulmonary rehabilitation after hospitalization
• Noninvasive PPV in severe chronic hypercapnia
• Pneumococcal and annual influenza vaccination