Editors: Susla, Gregory M.; Suffredini, Anthony F.; McAreavey, Dorothea; Solomon, Michael A.; Hoffman, William D.; Nyquist, Paul; Ognibene, Frederick P.; Shelhamer, James H.; Masur, Henry
Title: Handbook of Critical Care Drug Therapy, 3rd Edition
> Table of Contents > Chapter 4 - Pulmonary Therapies
Chapter 4
Pulmonary Therapies

TABLE 4.1. Asthma—Therapeutic Options
Agents Dosage
Inhaled β Agonists
Albuterol 2.5 mg (0.5 ml) diluted in 2–3 ml 0.9% NaCl q2–6h
10–15 mg/h (2–3 ml) diluted to a minimum of 4 ml at gas flow of 6–8 L/min (see Table 4.4)
Levalbuterol 0.63–1.25 mg
q2–6h
Subcutaneous β Agonists
Epinephrine 0.3 mg (0.3 ml)
Terbutaline 0.25 mg (0.25 ml)
Anticholinergic Agents See Tables 4.2 and 4.3
Theophylline See Table 4.5
Corticosteroids
Methylprednisolone or 60–125 mg q6–8h
Hydrocortisone or 2 mg/kg q4h
Hydrocortisone 2 mg/kg then 0.5 mg/kg/h
Inhaled Corticosteroids
Beclomethasone 40–160 µg twice daily
Budesonide 200–800 µg twice daily
Flunisolide 500–1,000 µg twice daily
Fluticasone MDI: 88–220 µg twice daily
PWD: 100–1,000 µg twice daily
Triamcinolone 200 µg 3 to 4 times daily or 400 µg twice daily
IV, intravenous; MDI, metered dose inhaler; PO, by mouth; PWD, powder
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Route Formulation Comment
Nebulized
Continuous nebulization		 0.5% solution
0.5% solution		 The frequency of intermittent β agonist administration will vary with the severity of illness of the patient; in severely ill patients, the initial interval may be hourly
Nebulized 0.63 mg/3 ml
1.25 mg/3 ml		 No greater benefit over albuterol in acutely ill, critically ill, or mechanically ventilated patients; clinical effects similar to albuterol
Subcutaneous 1:1000 solution May be considered in patients who do not respond to inhaled β agonists; may repeat dose every 15 min as needed up to 3 doses
Subcutaneous 1 mg/ml A second dose may be given after 20 min if necessary
IV/PO    
IV 40, 62.5 mg/ml  
IV 50 mg/ml  
IV
Continuous infusion		    
MDI MDI: 40, 80 µg/puff May be considered as an adjunct to systemic steroid therapy initially; initial dose may be higher
MDI MDI: 200 µg/puff  
MDI MDI: 250 µg/puff  
MDI, Rotadisk
Diskus		 MDI: 44, 110, 220 µg/puff
PWD: 50, 100, 250 µg/puff		  
MDI MDI: 100 µg/puff  
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TABLE 4.2. Antibronchospastic Agents—Metered Dose Inhalers
Agent β2/β1 Potency Dose Per Actuation Recommended Dosage/Interval
Inhaled β-Adrenergic Agents
Albuterol ++++/± 90 µg* 1–2 puffs q2–6h
Salmeterola See note    
Anticholinergic Agents
Ipratropium bromide — 18 µg 2–4 puffs q2–6h
Albuterol and ipratropium ++++/±
—		 90 µg*
18 µg		 2 puffs, 4× daily
Tiotropium — 18 µg One capsule, inhaled once daily
Individual capsules used for each dose
The dosing interval may vary depending on the severity of illness of the patient. The dose may need to be higher for patients on mechanical ventilation (i.e., 4–8 puffs q2–6h).
aSalmeterol is indicated for prophylactic use in chronic stable asthma and is not recommended for the treatment of acute bronchospasm. For maintenance of bronchodilatation and prevention of the symptoms of asthma, the usual dose is 2 puffs (42 µg) twice (in the morning and evening) daily.
*Dose delivered in terms of 90 µg of albuterol base.
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TABLE 4.3. Antibronchospastic Agents—Nebulized Drugs
Agent β2/β1 Potency Formulations Dosage
β-Adrenergic Agentsa
Albuterol ++++/± 0.5% solution 2.5–5 mg diluted in 2–3 ml 0.9% NaCl q2–6h
      Continuous nebulization; see Table 4.4
Levalbuterol ++++/± 0.63 mg/3 ml
1.25 mg/3 ml		 0.63–1.25 mg q2–6h
Anticholinergic Agents
Ipratropium bromide — 0.02% solution 500 µg diluted in 2–5 ml 0.9% NaCl q6–8h
Albuterol and Ipratropium ++++/±
—		 Ipratropium 0.5 mg and albuterol 3 mg/3 ml 3 ml q6h
Atropine Sulfate — 1 mg/ml injectable preparation 2.5–5 mg diluted in 2–3 ml 0.9% NaCl q3–5h
Glycopyrrolate — 0.2 mg/ml injectable preparation 2 mg diluted in 2–3 ml 0.9% NaCl q6h
aDosing interval depends on the status of the patient, but in severe asthma it may be as frequent as q1–2h under medical supervision.
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TABLE 4.4. Antibronchospastic Agents—Continuous Nebulization
Use the guidelines below (±20%) for 1 hour of nebulization. For prescribed dose of 10 mg/h at 15 L/min flow, add 2 mL albuterol (5 mg/mL) to 48 mL saline for 50 mL/h output. For multiple hours of operation, multiply by the number of hours desired.
Continuous Nebulizer—HEART®
  High Flow
Desired dose (mg/h) 5 10 15 5 10 15
Albuterol 5 mg/mL (mL) 1 2 3 1 2 3
Saline (mL) 29 28 27 49 48 47
Flow rate = Output 10 L/min = 30 mL/h 15 L/min = 50 mL/h
Continuous Nebulizer—UniHEART—IV™
  Low Flow
Desired dose (mg/h) 5 10 15 5 10 15
Albuterol 5 mg/mL (mL) 1 2 3 1 2 3
Saline (mL) 3 2 1 8 7 6
Flow rate = Output 2 L/min = 4 mL/h 4 L/min = 9 mL/h
Continuous Nebulizer—MiniHEART®
  Very Low Flow
Desired dose (mg/h) 2.5 5 7.5 10 12.5 15
Albuterol 5 mg/mL (mL) 0.5 1 1.5 2 2.5 3
Saline (mL) 7.5 7 6.5 6 5.5 5
Flow rate = Output 2 L/min = 8 mL/h
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TABLE 4.5. Theophylline/Aminophylline—Dosing
  Theophylline Aminophylline Comments
Loading Doses
No prior theophylline or aminophylline 5 mg/kg IV over 30 min 6 mg/kg IV over 30 min Theophylline = 80% × aminophylline
Loading dose administered over 30 min
Prior theophylline or aminophylline Estimate Estimate Theophylline 1 mg/kg IV/PO increases the serum concentration 2 mg/L; aminophylline 1.2 mg/kg IV/PO increases the serum concentration 2 mg/L; therapeutic range 10–20 mg/L
Maintenance Infusion
Adults (smokers) 0.72 mg/kg/h 0.9 mg/kg/h Maximum doses: theophylline 900 mg/d, aminophylline 1,080 mg/d
Adults (nonsmokers) 0.48 mg/kg/h 0.6 mg/kg/h  
Adults (heart failure, liver disease, cor pulmonale) 0.24 mg/kg/h 0.3 mg/kg/h Maximum doses: theophylline 400 mg/d, aminophylline 480 mg/d
IV, intravenous; PO, by mouth
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TABLE 4.6. Theophylline/Aminophylline–Drug Interactions
Drugs that Decrease Theophylline/Aminophylline Clearance/Metabolism (Serum Levels Rise) Drugs that Increase Theophylline/Aminophylline Clearance/Metabolism (Serum Levels Fall) Drugs whose Activity is Decreased by Theophylline/Aminophylline
Amiodarone Carbamazepine Adenosine
Cimetidine Pentobarbital Benzodiazepines
Ciprofloxacin Phenobarbital Hydantoins
Clarithromycin
Disulfiram
Enoxacin		 Phenytoin
Rifampin
Rifabutin		 Nondepolarizing neuromuscular blocking agents
Erythromycin Ritonavir  
Fluvoxamine Ticlopidine  
Interferon    
Ketoconazole    
Mexiletine    
Norfloxacin    
Oral contraceptives    
Propranolol    
Troleandomycin    
Verapamil    
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TABLE 4.7. Upper Airway Obstruction—Nonspecific Therapies
Therapy Indication Dosage/Route Comments
Helium 80%–oxygen 20% mixture Partially obstructed airway Inhalation Limits FiO2 to maximum O2 concentration in mixture
Decreases turbulence of airflow
Helium/oxygen also available in helium 70%—oxygen 30% mixture
Dexamethasone Decreases airway edema 4–10 mg IV q6h Antitumor effect on certain anterior mediastinal tumors
Prophylactic for postextubation trauma, surgical trauma; efficacy controversial
Radiation Shrinks tumor   Anterior mediastinal tumors; tissue diagnosis may be required
Racemic epinephrine Decreases swelling of airway mucosa 0.5 ml of 2.25% solution in 2–5 ml 0.9% NaCl inhaled q1–4h prn Vasoconstrictor; may precipitate angina
Endotracheal intubation Fully obstructed airway
Partially obstructed airway and respiratory failure
Prohibitively increased work of breathing		 Oral or nasal endotracheal intubation
Surgical access: cricothyroidot- omy (for rapid access) or tracheostomy		 Technique of choice depends on experience of operator, although surgical access may be required
Caution: sedatives, anesthetics, or neuromuscular blockade may convert a partially obstructed airway to a totally obstructed airway
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TABLE 4.8. Mucolytic Agents
Agent Formulations Dosage/Interval/Comments
N-acetylcysteine 10%, 20% solutions Nebulization: 3–5 ml of 20% solution or 6–10 ml of 10% solution tid or qid
Instillation: 1–2 ml of 10% or 20% solution tid or qid
Administer after aerosolized β agonist to prevent bronchospasm
20% solution of N-acetylcysteine should be diluted 1:1 with normal saline
Dornase α recombinant 2.5 ml ampule containing 1 mg/ml Nebulization: 2.5 ml qd using a recommended nebulizer. (Hudson T Up-draft II and disposable jet nebulizer, Marquest Acorn II in conjunction with Pulmo-Aide compressor, Pari LC Jet+ nebulizer in conjunction with the Pari PRONEB compressor)
The effects of dornase α on respiratory tract infections in cystic fibrosis patients >21 years old may be smaller than younger patients, and twice daily dosing may be required in these patients
Dornase α may be continued or initiated during acute respiratory exacerbations, although the benefit of dornase α during acute respiratory exacerbations is unknown
Saturated solution of potassium iodide (SSKI) 1 g/ml 0.3–0.6 ml (300–600 mg) PO tid or qid
Guaifenesin 100 mg/5 ml, 200 mg/5 ml solutions 100–400 mg PO qid
PO, by mouth
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TABLE 4.9. Sclerosing Agents for Pleurodesis
Agent Dosage Dilution Comments/Side Effects
Doxycycline 500–1,000 mg 0.9% NaCl 25–100 ml Fever, chest pain
Talc insufflation 2–10 g   Pain, fever, hypotension; talc insufflation may be done in conjunction with thoracoscopy
Antineoplastic Agents
Bleomycin 60 U 0.9% NaCl 50–100 ml Do not exceed 40 U/m2 in elderly patients, significant systemic absorption, GI side effects, pain, fever
Cisplatin and cytarabine Cisplatin 100 mg/m2 and cytarabine 1,200 mg (mixed together) 0.9% NaCl 250 ml Use depends on antineoplastic activity rather than on irritative properties; myelosup- pression; GI side effects
Doxorubicin 10–100 mg 0.9% NaCl 10–100 ml Increased toxicity compared with tetracyclines, pain, fever, nausea, vomiting
Fluorouracil 2–3 g 0.9% NaCl 50–100 ml Leukopenia 7–10 d after instillation
Mechlorethamine 10–30 mg 0.9% NaCl 10–100 ml Increased toxicity compared with tetracyclines, nausea, vomiting, pain, fever, leukopenia
Thiotepa 0.6–0.8 mg/kg 0.9% NaCl 50–100 ml Less irritating than other agents
GI, gastrointestinal
Local anesthetics such as 1% lidocaine may be added to the sclerosing solution to reduce pain (up to a total dose of 400 mg).
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TABLE 4.10. Loculated Pleural Effusion—Thrombolytic Therapy
Agent Dosage Comments
Alteplase, recombinant 2–50 mg in 50–120 ml 0.9% NaCl Pleuritic chest pain may be treated with analgesics
Risk of bleeding complications, avoid concurrent anticoagulation
Most common adult dose is 50 mg
Directions for use:
  1. The optimal dosage of thrombolytic agent, duration of therapy, and effectiveness remain to be determined.
  2. The volume of agent administered should be adjusted based on the size of the effusion.
  3. After the agent is instilled into the pleural space, the chest tube should be clamped and the patient rotated in several positions to permit adequate drug distribution throughout the pleural space.
  4. The chest tube should remain clamped for 0.5 to 4 hours.
  5. After the chest tube is unclamped, the chest tube should be put on suction and the contents of the pleural space evacuated.
  6. The volume of the fluid returned should be determined. (Note: the volume of the dose instilled must be subtracted from the volume returned.)
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TABLE 4.11. Pulmonary Embolism—Therapy
Agent Loading Dosage Maintenance Dosage Comments
Anticoagulants
Heparin sulfate 80 U/kg IV bolus 18 U/kg/h for at least 7 d Check aPTT 6 h after therapy initiated; maintain aPTT 1.5–2.5 × baseline
Heparin clearance is increased in pulmonary embolism compared with deep venous thrombosis
Contraindicated in patients with active bleeding or heparin- induced thrombocytopenia and thrombosis
See Table 8.7 for weight-based dosing.
Warfarin 5–10 mg/d 2–7.5 mg/d Therapy may start on the 2nd day of heparinization
Dosage should be adjusted to maintain PT 1.5–2 × baseline PT (INR 2–3)
Use for 3–6 m to prevent recurrent pulmonary emboli unless there are persisting risk factors for hemorrhage
Contraindicated in patients with active bleeding and in pregnancy
Decrease loading and maintenance in presence of liver disease.
See Table 8.6
Enoxaparin — 1 mg/kg q12h Warfarin therapy started on day 1 of therapy
No need to monitor aPTT
Equally effective with less risk of bleeding compared with unfractionated heparin
Tinzaparin — 175 anti-Xa U/kg daily Treatment for at least 5 d until anticoagulated with warfarin
Thrombolyticsa     Indications include severe hypoxemia or hemodynamic instability
See Table 8.7
Recombinant tissue plasminogen activator (rtPA) 100 mg IV over 2 h   Contraindicated in patients with active bleeding, severe hypertension, trauma, recent stroke or surgery, or any hemorrhagic disease
aPTT, activated partial thromboplastin time; INR, international normalization ratio; IV, intravenous; PT, prothrombin time
aThe conventional indication for thrombolytic therapy is “massive” pulmonary embolism, characterized by one or more of the following abnormalities: (a) angiographic evidence of pulmonary artery occlusion of at least 40%; (b) hypotension with systolic arterial pressure <90–100 mm Hg; (c) syncope; (d) echocardiographic evidence of right ventricular dysfunction.