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

Definition

• PEFR or FEV1 does not increase to >40% of predicted with treatment
• Rising PaCO2 without improvement in airflow obstruction indices
• Development of a major complication: pneumothorax, pneumomediastinum, acute myocardial ischemia, or cardiac tachyarrhythmia (other than sinus tachycardia)

Pathophysiology Key Point

Critical warning sign: A normal or near-normal PCO2 in a patient in respiratory distress signals impending respiratory failure and the need for mechanical ventilation.

Management: Step-by-Step (Harrison's Approach)

Step 1 - Outpatient/Mild-Moderate Deterioration

• Beta2-agonist (e.g., albuterol) up to every 1 hour
• Consider increasing ICS dose 4-5x
• If hourly beta2-agonist needed for several hours → refer for urgent care

Step 2 - Urgent Care Setting

• Assess PEFR or FEV1
• Nebulized beta2-agonists up to every 20 minutes
• Supplemental oxygen to correct hypoxemia
• Add nebulized anticholinergics (ipratropium) for additional bronchodilation
• If PEFR >60% predicted: beta2-agonists alone often work; if fail to respond in 1-2 h → IV corticosteroids
• Sometimes add: LTRA, magnesium sulfate

Step 3 - Failure to Respond / Status Asthmaticus

In-Hospital Treatment:

Mechanical Ventilation in Status Asthmaticus

• Low respiratory rates and/or low tidal volumes to decrease peak airway pressures
• Permissive hypercapnia: allow PCO2 to rise intentionally
  • If critical acidosis: correct temporarily with IV sodium bicarbonate to raise pH
• Neuromuscular paralysis may sometimes be beneficial
• Bronchoscopy to clear mucus plugs has been described but is dangerous in this setting - use with extreme caution

High-Risk Patients for Asthma Mortality (Table 298-6)

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

Summary Algorithm

Mild-Moderate Attack
    └─> Beta2-agonist q1h + ↑ICS 4-5x
        └─> Hourly beta2-agonist for hours → Urgent care
                └─> PEFR/FEV1 assessment
                    ├─> PEFR >60%: Nebulized beta2-agonist q20 min
                    │       └─> No response in 1-2h → IV steroids
                    └─> PEFR <60% or no response in 4-6h → ADMIT
                            └─> Continuous bronchodilators + IV steroids
                                + IV aminophylline + O2 + Mg2+
                                    └─> PCO2 rising → Prepare for MV
                                            └─> Permissive hypercapnia
                                                + Low rate/volume strategy

• Harrison's Principles of Internal Medicine, 22nd Ed. (2025), Chapter 298 - Asthma, pp. 2269-2270 (ASTHMA ATTACKS / HIGH-RISK ASTHMA PATIENTS sections)
• Goldman-Cecil Medicine, Chapter 75 - Status Asthmaticus section, p. 888

Guillain-Barré Syndrome (GBS) - Harrison's Principles of Internal Medicine, 22nd Ed.

Definition & Epidemiology

• Incidence: 10-20 cases per million per year; ~5,000-6,000 cases/year in the USA
• Males slightly more affected than females
• Adults more frequently affected than children (in Western countries)
• Occurs year-round

Antecedent Events / Triggers

Note: mRNA COVID vaccines do NOT carry increased GBS risk.

Clinical Manifestations

• Rapidly evolving areflexic motor paralysis with or without sensory disturbance
• Ascending paralysis - often described as "rubbery legs" first
• Weakness evolves over hours to a few days
• Tingling dysesthesias in extremities
• Legs > arms; facial paresis in 50%
• Lower cranial nerve involvement - bulbar weakness (difficulty handling secretions, maintaining airway)
• Pain (neck, shoulder, back, spine) in ~50% in early stages
• Deep tendon reflexes - attenuate or disappear within first few days
• Large-fiber sensory functions (proprioception, DTRs) more severely affected than cutaneous sensation
• Bladder dysfunction - may occur in severe cases, usually transient
• Fever and constitutional symptoms absent at onset (if present, doubt the diagnosis)
• Weakness reaches nadir in 2-4 weeks, then plateau

Warning: ~30% of patients require ventilatory assistance, especially those with:

• Severe weakness on admission
• Rapid progression
• Facial and/or bulbar weakness in the first week

Subtypes and Associated Autoantibodies (Harrison's Fig. 458-1)

Pathophysiology

• Molecular mimicry: Immune response to antecedent infection cross-reacts with peripheral nerve components
• In AIDP: T cell-mediated + antibody/complement-mediated attack on Schwann cell surface and myelin
• In AMAN: Antibodies (anti-GM1, anti-GD1a) attack axolemma at nodes of Ranvier - no demyelination
• Anti-GQ1b antibodies: Found in >90% of MFS; GQ1b is highly expressed in extraocular motor nerves - explains selective ophthalmoplegia
• Earliest pathologic finding: activated macrophages penetrate the basement membrane of Schwann cells

Investigations

CSF (Lumbar Puncture) - Classic Finding

• Cytoalbuminous dissociation (albuminocytologic dissociation):
  • Elevated protein (often >45 mg/dL, may reach 100-1000 mg/dL)
  • Normal or near-normal white cell count (<10 cells/μL)
• CSF may be normal in the first week

Electrodiagnostic Studies (NCS/EMG)

• AIDP: Reduced conduction velocity, prolonged distal latencies, conduction block, absent F-waves (demyelinating pattern)
• AMAN/AMSAN: Reduced CMAP amplitudes, preserved conduction velocity (axonal pattern)
• Sural nerve "spared" pattern (sural sparing with absent median sensory)

Serology

• Anti-GQ1b (MFS), Anti-GM1/GD1a (AMAN), NCS, CBC, electrolytes, renal/liver function, LFTs
• HIV testing if risk factors

Diagnostic Criteria (Brighton/WHO Criteria per Harrison's)

Level 1 (Highest certainty) - GBS:

• Bilateral flaccid limb weakness
• Decreased/absent DTRs in weak limbs
• Monophasic illness; onset to nadir: 12 hours to 28 days; then clinical plateau
• Albuminocytologic dissociation: CSF WBC <50 cells/μL + elevated CSF protein
• Electrodiagnostic evidence consistent with GBS
• No alternative diagnosis

Level 2:

• Same motor findings + monophasic pattern + CSF WBC <50 (with or without protein elevation) OR EDx consistent
• No alternative diagnosis

Level 3 (Lowest certainty):

• Bilateral flaccid limb weakness + decreased DTRs + monophasic pattern
• No alternative diagnosis (no CSF/EDx required)

Miller Fisher Syndrome Diagnosis (Level 1):

• Bilateral ophthalmoparesis + bilateral reduced/absent DTRs + ataxia
• Absence of limb weakness
• Monophasic; onset to nadir: 12 h to 28 days
• Albuminocytologic dissociation + normal/sensory-only NCS
• No corticospinal signs, no altered consciousness
• No alternative diagnosis

Treatment

Specific Immunotherapy - Two equivalent options:

Key points:

• IVIg and PLEX are equally effective - neither is superior
• Combination is NOT more effective than either alone
• Corticosteroids are NOT beneficial (not recommended)
• Lack of noticeable improvement after one treatment is NOT an indication to try the other (except if patient worsened then stabilized)
• Treatment most effective if started within 2 weeks of onset

Supportive Care (Critical - ICU Monitoring Required):

• Vital capacity monitoring - serial measurements (intubate if VC <15-20 mL/kg or <1 L)
• Cardiac monitoring (arrhythmias from autonomic instability)
• Blood pressure monitoring (autonomic dysfunction - labile BP)
• DVT prophylaxis (heparin + compression stockings)
• Nutrition support
• Chest physiotherapy
• Tracheotomy: consider after 2 weeks of intubation
• Daily range-of-motion exercises (prevent joint contractures)
• Pain management (gabapentin, carbamazepine, opioids for neuropathic pain)
• Psychological support and reassurance

Prognosis

• ~85% achieve full functional recovery within several months to 1 year
• Mortality <5% in optimal care settings (usually from pulmonary complications)
• 5-10% have one or more late relapses - may be reclassified as CIDP

Poor Prognostic Factors:

• Severe proximal motor and sensory axonal damage
• Advanced age
• Fulminant or severe attack
• Delay in onset of treatment
• Elevated serum neurofilament light (NfL) chains
• High titers of anti-GM1 antibodies (more axonal involvement)

Autonomic Dysfunction

• Sinus tachycardia (most common)
• Bradycardia, heart block
• Labile blood pressure
• Urinary retention
• Paralytic ileus
• Orthostatic hypotension