Respiratory Failure Medication
- Author: Ata Murat Kaynar, MD; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM more...
Pharmacotherapy for cardiogenic pulmonary edema and acute exacerbations of chronic obstructive pulmonary disease (COPD) is discussed here. The goals of therapy in cardiogenic pulmonary edema are to achieve a pulmonary capillary wedge pressure of 15-18 mm Hg and a cardiac index greater than 2.2 L/min/m2 while maintaining adequate blood pressure and organ perfusion. These goals may have to be modified for some patients. Diuretics, nitrates, analgesics, and inotropes are used in the treatment of acute pulmonary edema.
First-line therapy generally includes a loop diuretic such as furosemide, which inhibits sodium chloride reabsorption in the ascending loop of Henle.
Administer loop diuretics such as furosemide intravenously (IV) because this allows both superior potency and a higher peak concentration despite an increased incidence of adverse effects, particularly ototoxicity.
Metolazone has been used as adjunctive therapy in patients initially refractory to furosemide. It has been demonstrated to be synergistic with loop diuretics in treating refractory patients and causes a greater loss of potassium. Metolazone is a potent thiazide-related diuretic that sometimes is used in combination with furosemide for more aggressive diuresis. It is also used for initiating diuresis in patients with a degree of renal dysfunction.
Nitrates reduce myocardial oxygen demand by lowering preload and afterload. In severely hypertensive patients, nitroprusside causes more arterial dilatation than nitroglycerin. Nevertheless, in view of the possibility of thiocyanate toxicity and the coronary steal phenomenon associated with nitroprusside, IV nitroglycerin may be the initial therapy of choice for afterload reduction.
Sublingual nitroglycerin tablets and spray are particularly useful in the patient who presents with acute pulmonary edema with a systolic blood pressure of at least 100 mm Hg. As with sublingual nitroglycerin tablets, the onset of action of nitroglycerin spray is 1-3 minutes, with a half-life of 5 minutes. Administration of the spray may be easier, and it can be stored for as long as 4 years.
Topical nitrate therapy is reasonable in a patient presenting with class I-II congestive heart failure (CHF). However, in patients with more severe signs of heart failure or pulmonary edema, IV nitroglycerin is preferred because it is easier to monitor hemodynamics and absorption, particularly in patients with diaphoresis. Oral nitrates, because of their delayed absorption, play little role in the management of acute pulmonary edema.
Nitroprusside produces vasodilation of venous and arterial circulation. At higher dosages, it may exacerbate myocardial ischemia by increasing heart rate. It is easily titratable.
Morphine IV is an excellent adjunct in the management of acute pulmonary edema. In addition to anxiolysis and analgesia, its most important effect is venodilation, which reduces preload. It also causes arterial dilatation, which reduces systemic vascular resistance and may increase cardiac output.
Morphine sulfate is the drug of choice for narcotic analgesia because of its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Morphine sulfate administered IV may be dosed in a number of ways and commonly is titrated until the desired effect is obtained.
The principal inotropic agents are dopamine, dobutamine, inamrinone (formerly amrinone), milrinone, dopexamine, and digoxin. In patients with hypotension who present with CHF, dopamine and dobutamine usually are employed. Inamrinone and milrinone inhibit phosphodiesterase, resulting in increased intracellular cyclic adenosine monophosphate (cAMP) and altered calcium transport. As a result, they increase cardiac contractility and reduce vascular tone by vasodilatation.
Dopamine is a positive inotropic agent that stimulates both adrenergic and dopaminergic receptors. Its hemodynamic effects depend on the dose. Lower doses stimulate mainly dopaminergic receptors that produce renal and mesenteric vasodilation; higher doses produce cardiac stimulation and renal vasodilation. Doses of 2-10 µg/kg/min can lead to tachycardia, ischemia, and dysrhythmias. Doses higher than 10 µg/kg/min cause vasoconstriction, which increases afterload.
Norepinephrine is used in protracted hypotension after adequate fluid replacement. It stimulates beta1- and alpha-adrenergic receptors, which leads to increased cardiac muscle contractility and heart rate, as well as vasoconstriction. As a result, norepinephrine increases systemic blood pressure and cardiac output. Adjust and maintain infusion to stabilize blood pressure (eg, 80-100 mm Hg systolic) sufficiently to perfuse vital organs.
Dobutamine produces vasodilation and increases the inotropic state. At higher dosages, it may cause increased heart rates, thus exacerbating myocardial ischemia. It is a strong inotropic agent with minimal chronotropic effect and no vasoconstriction.
Bronchodilators are an important component of treatment in respiratory failure caused by obstructive lung disease. These agents act to decrease muscle tone in both small and large airways in the lungs. This category includes beta-adrenergics, methylxanthines, and anticholinergics.
Terbutaline acts directly on beta2 receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance.
Albuterol is a beta-agonist useful in the treatment of bronchospasm. It selectively stimulates beta2-adrenergic receptors of the lungs. Bronchodilation results from relaxation of bronchial smooth muscle, which relieves bronchospasm and reduces airway resistance.
Xanthine derivatives may relax smooth muscle of the bronchi.
Theophylline has a number of physiologic effects, including increases in collateral ventilation, respiratory muscle function, mucociliary clearance, and central respiratory drive. It partially acts by inhibiting phosphodiesterase, elevating cellular cAMP levels, or antagonizing adenosine receptors in the bronchi, resulting in relaxation of smooth muscle. However, its clinical efficacy is controversial, especially in the acute setting.
Anticholinergics antagonize the action of acetylcholine with muscarinic receptor on bronchial smooth muscle.
Ipratropium bromide is an anticholinergic medication that appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine, specifically with the muscarinic receptor on bronchial smooth muscle. Vagal tone can be significantly increased in COPD; therefore, this can have a profound effect. Ipratropium can be combined with a beta-agonist because it may require 20 minutes to begin having an effect.
Corticosteroids have been shown to be effective in accelerating recovery from acute COPD exacerbations and are an important anti-inflammatory therapy in asthma. Although they may not make a clinical difference in the emergency department (ED), they have some effect 6-8 hours into therapy; therefore, early dosing is critical.
Methylprednisolone is usually given IV in the ED for initiation of corticosteroid therapy, although in theory, oral administration should be equally efficacious.
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