4 - Pulmonary Therapies

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

Copyright 2006 Lippincott Williams & Wilkins

> Table of Contents > Chapter 4 - Pulmonary Therapies

Chapter 4

Pulmonary Therapies

TABLE 4.1. Asthma Therapeutic Options

Agents	Dosage
Inhaled 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 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 g twice daily
Budesonide	200 800 g twice daily
Flunisolide	500 1,000 g twice daily
Fluticasone	MDI: 88 220 g twice daily PWD: 100 1,000 g twice daily
Triamcinolone	200 g 3 to 4 times daily or 400 g 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 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 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 g/puff	May be considered as an adjunct to systemic steroid therapy initially; initial dose may be higher
MDI	MDI: 200 g/puff
MDI	MDI: 250 g/puff
MDI, Rotadisk Diskus	MDI: 44, 110, 220 g/puff PWD: 50, 100, 250 g/puff
MDI	MDI: 100 g/puff

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TABLE 4.2. Antibronchospastic Agents Metered Dose Inhalers

Agent	2/ 1 Potency	Dose Per Actuation	Recommended Dosage/Interval
Inhaled -Adrenergic Agents
Albuterol	++++/	90 g*	1 2 puffs q2 6h
Salmeterola	See note
Anticholinergic Agents
Ipratropium bromide		18 g	2 4 puffs q2 6h
Albuterol and ipratropium	++++/	90 g* 18 g	2 puffs, 4 daily
Tiotropium		18 g	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 g) twice (in the morning and evening) daily. *Dose delivered in terms of 90 g of albuterol base.

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TABLE 4.3. Antibronchospastic Agents Nebulized Drugs

Agent	2/ 1 Potency	Formulations	Dosage
-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 g 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 agonist to prevent bronchospasm 20% solution of N-acetylcysteine should be diluted 1:1 with normal saline
Dornase 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 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 may be continued or initiated during acute respiratory exacerbations, although the benefit of dornase 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: The optimal dosage of thrombolytic agent, duration of therapy, and effectiveness remain to be determined. The volume of agent administered should be adjusted based on the size of the effusion. 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. The chest tube should remain clamped for 0.5 to 4 hours. After the chest tube is unclamped, the chest tube should be put on suction and the contents of the pleural space evacuated. 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.