Rabu, 21 November 2007

Respiratory Failure

Background: Respiratory failure is a syndrome in which the respiratory system fails in one or both of its gas exchange functions: oxygenation and carbon dioxide elimination. In practice, respiratory failure is defined as a PaO2 value of less than 60 mm Hg while breathing air or a PaCO2 of more than 50 mm Hg. Furthermore, respiratory failure may be acute or chronic. While acute respiratory failure is characterized by life-threatening derangements in arterial blood gases and acid-base status, the manifestations of chronic respiratory failure are less dramatic and may not be as readily apparent.

Classification of respiratory failure

Respiratory failure may be classified as hypoxemic or hypercapnic and may be either acute or chronic.

Hypoxemic respiratory failure (type I) is characterized by a PaO2 of less than 60 mm Hg with a normal or low PaCO2. This is the most common form of respiratory failure, and it can be associated with virtually all acute diseases of the lung, which generally involve fluid filling or collapse of alveolar units. Some examples of type I respiratory failure are cardiogenic or noncardiogenic pulmonary edema, pneumonia, and pulmonary hemorrhage.

Hypercapnic respiratory failure (type II) is characterized by a PaCO2 of more than 50 mm Hg. Hypoxemia is common in patients with hypercapnic respiratory failure who are breathing room air. The pH depends on the level of bicarbonate, which, in turn, is dependent on the duration of hypercapnia. Common etiologies include drug overdose, neuromuscular disease, chest wall abnormalities, and severe airway disorders (eg, asthma, chronic obstructive pulmonary disease [COPD]).

Distinctions between acute and chronic respiratory failure

Acute hypercapnic respiratory failure develops over minutes to hours; therefore, pH is less than 7.3. Chronic respiratory failure develops over several days or longer, allowing time for renal compensation and an increase in bicarbonate concentration. Therefore, the pH usually is only slightly decreased.

The distinction between acute and chronic hypoxemic respiratory failure cannot readily be made on the basis of arterial blood gases. The clinical markers of chronic hypoxemia, such as polycythemia or cor pulmonale, suggest a long-standing disorder.

Pathophysiology: Respiratory failure can arise from an abnormality in any of the components of the respiratory system, including the airways, alveoli, CNS, peripheral nervous system, respiratory muscles, and chest wall. Patients who have hypoperfusion secondary to cardiogenic, hypovolemic, or septic shock often present with respiratory failure.

Hypoxemic respiratory failure: The pathophysiologic mechanisms that account for the hypoxemia observed in a wide variety of diseases are ventilation-perfusion (V/Q) mismatch and shunt. These 2 mechanisms lead to widening of the alveolar-arterial oxygen difference, which normally is less than 15 mm Hg. With V/Q mismatch, the areas of low ventilation relative to perfusion (low V/Q units) contribute to hypoxemia. An intrapulmonary or intracardiac shunt causes mixed venous (deoxygenated) blood to bypass ventilated alveoli and results in venous admixture. The distinction between V/Q mismatch and shunt can be made by assessing the response to oxygen supplementation or calculating the shunt fraction following inhalation of 100% oxygen. In most patients with hypoxemic respiratory failure, these 2 mechanisms coexist.

Hypercapnic respiratory failure: At a constant rate of carbon dioxide production, PaCO2 is determined by the level of alveolar ventilation (Va), where VCO2 is ventilation of carbon dioxide and K is a constant value (0.863).

    (Va = K x VCO2)/PaCO2

A decrease in alveolar ventilation can result from a reduction in overall (minute) ventilation or an increase in the proportion of dead space ventilation. A reduction in minute ventilation is observed primarily in the setting of neuromuscular disorders and CNS depression. In pure hypercapnic respiratory failure, the hypoxemia is easily corrected with oxygen therapy.

Ventilatory capacity versus demand

Ventilatory capacity is the maximal spontaneous ventilation that can be maintained without development of respiratory muscle fatigue. Ventilatory demand is the spontaneous minute ventilation that results in a stable PaCO2. Normally, ventilatory capacity greatly exceeds ventilatory demand. Respiratory failure may result from either a reduction in ventilatory capacity or an increase in ventilatory demand (or both). Ventilatory capacity can be decreased by a disease process involving any of the functional components of the respiratory system and its controller. Ventilatory demand is augmented by an increase in minute ventilation and/or an increase in the work of breathing.

Pathophysiologic mechanisms in acute respiratory failure

The act of respiration engages 3 processes: (1) transfer of oxygen across the alveolus, (2) transport of oxygen to the tissues, and (3) removal of carbon dioxide from blood into the alveolus and then into the environment. Respiratory failure may occur from malfunctioning of any of these processes. In order to understand the pathophysiologic basis of acute respiratory failure, an understanding of pulmonary gas exchange is essential.

Physiology of gas exchange

Respiration primarily occurs at the alveolar capillary units of the lungs, where exchange of oxygen and carbon dioxide between alveolar gas and blood takes place. Following diffusion into the blood, the oxygen molecules reversibly bind to the hemoglobin. Each molecule of hemoglobin contains 4 sites for combination with molecular oxygen, 1 g of hemoglobin combines with a maximum of 1.36 mL of oxygen. The quantity of oxygen combined with hemoglobin depends on the level of blood PaO2. This relationship, expressed as the oxygen hemoglobin dissociation curve, is not linear, but has a sigmoid-shaped curve with a steep slope between a PaO2 of 10 and 50 mm Hg and a flat portion above a PaO2 of 70 mm Hg. The carbon dioxide is transported in 3 main forms: (1) in simple solution, (2) as bicarbonate, and (3) combined with protein of hemoglobin as a carbamino compound.

During ideal gas exchange, blood flow and ventilation would perfectly match each other, resulting in no alveolar-arterial PO2 difference. However, even in normal lungs, not all alveoli are ventilated and perfused perfectly. For a given perfusion, some alveoli are underventilated while others are overventilated. Similarly, for known alveolar ventilation, some units are underperfused while others are overperfused. The optimally ventilated alveoli that are not perfused well are called high V/Q units (acting like dead space), and alveoli that are optimally perfused but not adequately ventilated are called low V/Q units (acting like a shunt).

Alveolar ventilation

At steady state, the rate of carbon dioxide production by the tissues is constant and equals the rate of carbon dioxide elimination by the lung. This relationship is expressed as PaCO2 = VCO2 x 0.862/Va. This relationship signifies whether the alveolar ventilation is adequate for metabolic needs of the body.

The efficiency of lungs at carrying out of respiration can be further evaluated by measuring alveolar-to-arterial PaO2 difference. This difference is calculated by the following equation:

    PaO2 = FIO2 x (PB – PH2O) – PaCO2/R

For the above equation, PaO2 = alveolar PO2, FIO2 = fractional concentration of oxygen in inspired gas, PB = barometric pressure, PH2O = water vapor pressure at 37°C, PaCO2 = alveolar PCO2, assumed to be equal to arterial PCO2, and R = respiratory exchange ratio. R depends on oxygen consumption and carbon dioxide production. At rest, VCO2/VO2 is approximately 0.8.

Even normal lungs have some degree of V/Q mismatching and a small quantity of right-to-left shunt, alveolar PO2 is slightly higher than arterial PO2. However, an increase in alveolar-to-arterial PO2 above 15-20 mm Hg indicates pulmonary disease as the cause of hypoxemia.

Pathophysiologic causes of acute respiratory failure

Hypoventilation, V/Q mismatch, and shunt are the most common pathophysiologic causes of acute respiratory failure. These are described in the following paragraphs.

Hypoventilation is an uncommon cause of respiratory failure and usually occurs from depression of the CNS from drugs or neuromuscular diseases affecting respiratory muscles. Hypoventilation is characterized by hypercapnia and hypoxemia. The relationship between PaCO2 and alveolar ventilation is hyperbolic. As ventilation decreases below 4-6 L/min, PaCO2 rises precipitously. Hypoventilation can be differentiated from other causes of hypoxemia by the presence of a normal alveolar-arterial PO2 gradient.

V/Q mismatch is the most common cause of hypoxemia. V/Q units may vary from low to high ratios in the presence of a disease process. The low V/Q units contribute to hypoxemia and hypercapnia in contrast to high V/Q units, which waste ventilation but do not affect gas exchange unless quite severe. The low V/Q ratio may occur either from a decrease in ventilation secondary to airway or interstitial lung disease or from overperfusion in the presence of normal ventilation. The overperfusion may occur in case of pulmonary embolism, where the blood is diverted to normally ventilated units from regions of lungs that have blood flow obstruction secondary to embolism. Administration of 100% oxygen eliminates all of the low V/Q units, thus leading to correction of hypoxemia. As hypoxemia increases the minute ventilation by chemoreceptor stimulation, the PaCO2 level generally is not affected.

Shunt is defined as the persistence of hypoxemia despite 100% oxygen inhalation. The deoxygenated blood (mixed venous blood) bypasses the ventilated alveoli and mixes with oxygenated blood that has flowed through the ventilated alveoli, consequently leading to a reduction in arterial blood content. The shunt is calculated by the following equation:

    QS/QT = (CCO2 – CaO2)/CCO2 – CVO2)

QS/QT is the shunt fraction, CCO2 (capillary oxygen content) is calculated from ideal alveolar PO2, CaO2 (arterial oxygen content) is derived from PaO2 using the oxygen dissociation curve, and CVO2 (mixed venous oxygen content) can be assumed or measured by drawing mixed venous blood from pulmonary arterial catheter.

Anatomical shunt exists in normal lungs because of the bronchial and thebesian circulations, accounting for 2-3% of shunt. A normal right-to-left shunt may occur from atrial septal defect, ventricular septal defect, patent ductus arteriosus, or arteriovenous malformation in the lung. Shunt as a cause of hypoxemia is observed primarily in pneumonia, atelectasis, and severe pulmonary edema of either cardiac or noncardiac origin. Hypercapnia generally does not develop unless the shunt is excessive (>60%). When compared to V/Q mismatch, hypoxemia produced by shunt is difficult to correct by oxygen administration.


  • In the US: Respiratory failure is a syndrome rather than a single disease process, and the overall frequency of respiratory failure is not well known. The estimates for individual diseases mentioned here can be found in the appropriate article.
Mortality/Morbidity: The mortality rate associated with respiratory failure varies according to the etiology. For acute respiratory distress syndrome, the mortality rate is approximately 50% in most studies. Acute exacerbation of COPD carries a mortality rate of approximately 30%. The mortality rates for other causative disease processes have not been well described.

Medical Care: Hypoxemia is the major immediate threat to organ function. Therefore, the first objective in the management of respiratory failure is to reverse and/or prevent tissue hypoxia. Hypercapnia unaccompanied by hypoxemia generally is well tolerated and probably is not a threat to organ function unless accompanied by severe acidosis. Many experts believe that hypercapnia should be tolerated until the arterial blood pH falls below 7.2. Appropriate management of the underlying disease obviously is an important component in the management of respiratory failure.

A patient with acute respiratory failure generally should be admitted to a respiratory care or intensive care unit. Most patients with chronic respiratory failure can be treated at home with oxygen supplementation and/or ventilatory assist devices along with therapy for their underlying disease.

  • Airway management
    • Assurance of an adequate airway is vital in a patient with acute respiratory distress.
    • The most common indication for endotracheal intubation (ETT) is respiratory failure.
    • ETT serves as an interface between the patient and the ventilator.
    • Another indication for ETT is airway protection in patients with altered mental status.
  • Correction of hypoxemia
    • After securing an airway, attention must turn to correcting the underlying hypoxemia, the most life-threatening facet of acute respiratory failure.
    • The goal is to assure adequate oxygen delivery to tissues, generally achieved with a PaO2 of 60 mm Hg or an arterial oxygen saturation (SaO2) of greater than 90%.
    • Supplemental oxygen is administered via nasal prongs or face mask; however, in patients with severe hypoxemia, intubation and mechanical ventilation often are required.
  • Coexistent hypercapnia and respiratory acidosis may need to be addressed. This is done by correcting the underlying cause or providing ventilatory assistance.
    • Mechanical ventilation is used for 2 essential reasons: (1) to increase PaO2 and (2) to lower PaCO2. Mechanical ventilation also rests the respiratory muscles and is an appropriate therapy for respiratory muscle fatigue.
  • Ventilator management
    • The use of mechanical ventilation during the polio epidemics of the 1950s was the impetus that led to the development of the discipline of critical care medicine.
    • Prior to the mid 1950s, negative-pressure ventilation with the use of iron lungs was the predominant method of ventilatory support.
    • Currently, virtually all mechanical ventilatory support for acute respiratory failure is provided by positive-pressure ventilation. Nevertheless, negative-pressure ventilation still is used occasionally in patients with chronic respiratory failure.
    • Over the years, mechanical ventilators have evolved from simple pressure-cycled machines to sophisticated microprocessor-controlled systems. A brief review of mechanical ventilation is presented as follows.
  • Overview of mechanical ventilation
    • Positive-pressure versus negative-pressure ventilation: In order for air to enter the lungs, a pressure gradient must exist between the airway and alveoli. This can be accomplished either by raising pressure at the airway (positive-pressure ventilation) or by lowering pressure at the level of the alveolus (negative-pressure ventilation). The iron lung or tank ventilator is the most common type of negative-pressure ventilator used in the past. These ventilators work by creating subatmospheric pressure around the chest, thereby lowering pleural and alveolar pressure, and thus facilitating flow of air into the patient's lungs. These ventilators are bulky, poorly tolerated, and are not suitable for use in modern critical care units. Positive-pressure ventilation can be achieved by an endotracheal or tracheostomy tube or noninvasively through a nasal mask or face mask.
    • Controlled versus patient-initiated (ie, assisted): Ventilatory assistance can be controlled (AC) or patient-initiated. In controlled modes of ventilation, the ventilator delivers assistance independent of the patient's own spontaneous inspiratory efforts. In contrast, during patient-initiated modes of ventilation, the ventilator delivers assistance in response to the patient's own inspiratory efforts. The patient's inspiratory efforts can be sensed either by pressure or flow-triggering mechanisms Triggering mechanism).
    • Pressure-targeted versus volume-targeted: During positive-pressure ventilation, either pressure or volume may be set as the independent variable. In volume-targeted (or volume preset) ventilation, tidal volume is the independent variable set by the physician and/or respiratory therapist, and airway pressure is the dependent variable. In volume-targeted ventilation, airway pressure is a function of the set tidal volume and inspiratory flow rate, the patient's respiratory mechanics (compliance and resistance), and the patient's respiratory muscle activity. In pressure-targeted (or pressure preset) ventilation, airway pressure is the independent variable and tidal volume is the dependent variable. The tidal volume during pressure-targeted ventilation is a complex function of inspiratory time, the patient's respiratory mechanics, and the patient's own respiratory muscle activity.


  • Consultation with a pulmonary specialist and an intensivist often are required.
  • Patients with acute respiratory failure or exacerbations of chronic respiratory failure need to be admitted to the intensive care unit for ventilatory support.


Patients generally are prescribed bed rest during early phases of respiratory failure management. However, ambulation as soon possible helps ventilate atelectatic areas of the lung.

The pharmacotherapy of cardiogenic pulmonary edema and acute exacerbations of 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 need to be modified for some patients. Diuretics, nitrates, analgesics, and inotropics are used in the treatment of acute pulmonary edema.
Drug Category: Diuretics -- First-line therapy generally includes a loop diuretic such as furosemide, which inhibits sodium chloride reabsorption in the ascending loop of Henle.
Drug Name
Furosemide (Lasix) -- Administer loop diuretics IV because this allows for both superior potency and a higher peak concentration despite increased incidence of adverse effects, particularly ototoxicity.
Adult Dose10-20 mg IV for patients symptomatic with CHF not already using diuretics
40-80 mg IV for patients already using diuretics
80-120 mg IV for patients whose symptoms are refractory to initial dose after 1 h of administration or who have significant renal insufficiency
Higher doses and more rapid redosing may be appropriate for patients in severe distress
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity, hepatic coma, anuria, state of severe electrolyte depletion
InteractionsMetformin decreases concentrations; conversely, furosemide interferes with the hypoglycemic effect of antidiabetic agents; also antagonizes muscle-relaxing effect of tubocurarine
Auditory toxicity appears to be increased with concurrent use of aminoglycoside and furosemide; hearing loss of varying degrees may occur
Anticoagulant activity of warfarin may be enhanced when taken concurrently
Increased plasma lithium levels and toxicity are possible when taken concurrently
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsMonitor for electrolyte imbalance; caution with coadministration of nephrotoxic drugs
Drug Name
Metolazone (Mykrox, Zaroxolyn) -- Has been used as adjunctive therapy in patients initially refractory to furosemide. Has been demonstrated to be synergistic with loop diuretics in treating refractory patients and causes a greater loss of potassium. Potent loop diuretic that sometimes is used in combination with Lasix for more aggressive diuresis. Also used in patients with a degree of renal dysfunction for initiating diuresis.
Adult Dose5-10 mg PO before redosing with furosemide
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity, hepatic coma, encephalopathy, anuria
InteractionsThiazides may decrease effect of anticoagulants, sulfonylureas, and gout medications; anticholinergics and amphotericin B may increase toxicity of thiazides; effects of thiazides may decrease when used concurrently with bile acid sequestrants, NSAIDs, and methenamine
When coadministered, thiazides increase toxicity of anesthetics, diazoxide, digitoxin, lithium, loop diuretics, antineoplastics, allopurinol, calcium salts, vitamin D, and nondepolarizing muscle relaxants
Pregnancy D - Unsafe in pregnancy
PrecautionsExercise caution with hepatic and renal disease, diabetes mellitus, gout, and systemic lupus erythematosus
Drug Category: Nitrates -- These agents reduce myocardial oxygen demand by lowering preload and afterload. In severely hypertensive patients, nitroprusside causes more arterial dilatation than nitroglycerin. Nevertheless, due to 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.
Drug Name
Nitroglycerin (Nitro-Bid, Nitrol) -- SL nitroglycerin and Nitrospray are particularly useful in the patient who presents with acute pulmonary edema with a systolic blood pressure of at least 100 mm Hg. Similar to SL, onset of Nitrospray is 1-3 min, with a half-life of 5 min. Administration of Nitrospray may be easier, and it can be stored for as long as 4 y. One study demonstrated significant and rapid hemodynamic improvement in 20 patients with pulmonary edema who were given Nitrospray. Topical nitrate therapy is reasonable in a patient presenting with class I-II 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, due to delayed absorption, play little role in the management of acute pulmonary edema.
Adult DoseNitrospray: 1 puff (0.4 mg) equivalent to a single 1/150 SL; may repeat q3-5min as hemodynamics permit, not to exceed 1.2 mg
Ointment: Apply 1-2 inches of nitropaste to chest wall
Injection: Start at 20 mcg/min IV and titrate to effect in 5- to 10-mcg increments q3-5min
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity, severe anemia, shock, postural hypotension, head trauma, closed-angle glaucoma, cerebral hemorrhage
InteractionsAspirin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur when coadministered with calcium channel blockers, adjustment in dose of either agent may be necessary
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsCaution in coronary artery disease and low systolic blood pressure
Drug Name
Nitroprusside sodium (Nitropress) -- Produces vasodilation of venous and arterial circulation. At higher dosages, may exacerbate myocardial ischemia by increasing heart rate. Easily titratable.
Adult Dose10-15 mcg/min IV; titrate to effective dose range of 30-50 mcg/min and a systolic blood pressure of at least 90 mm Hg
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity, subaortic stenosis, optic atrophy, tobacco amblyopia, idiopathic hypertrophic, atrial fibrillation or flutter
InteractionsPatients receiving other hypertensive therapy may be more sensitive to sodium nitroprusside
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsExercise caution with increased intracranial pressure, hepatic failure, severe renal impairment, and hypothyroidism.
In renal or hepatic insufficiency, levels may increase and can cause cyanide toxicity
Has potent effects on blood pressure (use only in those patients with mean arterial pressures >70 mm Hg)
Drug Category: Analgesics -- Morphine IV is an excellent adjunct in the management of acute pulmonary edema. In addition to being both an anxiolytic and an analgesic, its most important effect is venodilation, which reduces preload. Also causes arterial dilatation, which reduces systemic vascular resistance and may increase cardiac output.
Drug Name
Morphine sulfate (Duramorph, Astramorph, MS Contin) -- DOC for narcotic analgesia due to 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 desired effect is obtained.
Adult Dose2-5 mg and repeated q10-15min IV unless respiratory rate is <20>
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity, hypotension, potentially compromised airway with uncertain rapid airway control, respiratory depression, nausea, emesis, constipation, urinary retention
InteractionsPhenothiazine may antagonize analgesic effects of opiate agonists; tricyclic antidepressants, MAOIs, altered mental status, and other CNS depressants may potentiate adverse effects of morphine when used concurrently
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsExercise caution with atrial flutter and other supraventricular tachycardias; morphine has vagolytic action and may increase the ventricular response rate; due to addictive nature, abuse also is a possibility, although this is not a significant concern in a critically ill patient
Drug Category: Inotropics -- Principal inotropic agents include dopamine, dobutamine, inamrinone (formerly amrinone), milrinone, dopexamine, and digoxin. In patients with hypotension presenting with CHF, dopamine and dobutamine usually are employed. Inamrinone and milrinone inhibit phosphodiesterase, resulting in an increase of intracellular cyclic AMP and alteration in calcium transport. As a result, they increase cardiac contractility and reduce vascular tone by vasodilatation.
Drug Name
Dopamine (Intropin) -- Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effects depend on the dose. Lower doses stimulate mainly dopaminergic receptors that produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation are produced by higher doses. Positive inotropic agent at 2-10 mcg/kg/min that can lead to tachycardia, ischemia, and dysrhythmias. Doses >10 mcg/kg/min cause vasoconstriction, which increases afterload.
Adult Dose5 mcg/kg/min IV and increase at increments of 5 mcg/kg/min IV to dose of 20 mcg/kg/min
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity, pheochromocytoma, ventricular fibrillation
InteractionsPhenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects, thus, lower dosage
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsClosely monitor urine flow, cardiac output, pulmonary wedge pressure, and blood pressure during infusion; prior to infusion, correct hypovolemia with either whole blood or plasma, as indicated; monitoring of central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia
Drug Name
Norepinephrine (Levophed) -- Used in protracted hypotension following adequate fluid replacement. Stimulates beta1- and alpha-adrenergic receptors, which in turn increases cardiac muscle contractility and heart rate, as well as vasoconstriction. As a result, 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.
Adult Dose0.05-2 mcg/kg/min IV titrated according to hemodynamic response not to exceed 10 mcg/kg/min
Pediatric Dose0.05-0.1 mcg/kg/min IV titrated according to hemodynamic response; not to exceed 1-2 mcg/kg/min
ContraindicationsDocumented hypersensitivity; peripheral or mesenteric vascular thrombosis because ischemia may be increased and the area of the infarct extended
InteractionsAtropine sulfate may enhance the pressor response of norepinephrine by blocking the reflex bradycardia caused by norepinephrine; effects increase when administered concurrently with tricyclic antidepressants, MAOIs, antihistamines, guanethidine, methyldopa, and ergot alkaloids
Pregnancy D - Unsafe in pregnancy
PrecautionsCorrect hypovolemia before administering norepinephrine; extravasation may cause severe tissue necrosis; therefore, administer into large vein; use with caution in occlusive vascular disease
Drug Name
Dobutamine (Dobutrex) -- Produces vasodilation and increases inotropic state. At higher dosages, may cause increased heart rate, thus exacerbating myocardial ischemia. Strong inotropic agent with minimal chronotropic effect and no vasoconstriction.
Adult Dose2.5 mcg/kg/min IV initially; generally therapeutic in the range of 10-40 mcg/kg/min
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity, idiopathic hypertrophic subaortic stenosis, atrial fibrillation or flutter
InteractionsBeta-adrenergic blockers antagonize effects of nitroprusside; general anesthetics may increase toxicity
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsFollowing an MI, use dobutamine with caution; correct hypovolemia before using
Drug Category: Bronchodilators -- These agents 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.
Drug Name
Terbutaline (Brethaire, Bricanyl) -- Acts directly on beta2-receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance.
Adult Dose0.25 mg (0.25 cc of 1-mg/mL concentration) SC; not to exceed 0.5 mg SC q4h
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity, tachycardia resulting from cardiac arrhythmias
InteractionsConcomitant use with beta-blockers may inhibit bronchodilatory, cardiac, and vasodilatory effects of beta-agonists; coadministration of MAOIs with beta-sympathomimetics may result in severe hypertension, headache, and hyperpyrexia, which may result in a hypertensive crisis
MAOIs also may potentiate activity of beta-adrenergic agonists on vascular system
Coadministration of oxytocic drugs (eg, ergonovine with terbutaline) may result in severe hypotension
Pregnancy B - Usually safe but benefits must outweigh the risks.
PrecautionsCaution in coronary disease; through intracellular shifts, may decrease serum potassium levels, which can produce adverse cardiovascular effects; however, decrease usually is transient and may not require supplementation
Drug Name
Albuterol (Proventil) -- Beta-agonist useful in the treatment of bronchospasm. Selectively stimulate beta2-adrenergic receptors of the lungs. Bronchodilation results from relaxation of bronchial smooth muscle, which relieves bronchospasm and reduces airway resistance.
Adult Dose5 mg/mL of solution for nebulization, usually mixed as 0.5-1 cc with 2.5 cc of water and nebulized prn in acute setting
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity to albuterol, adrenergic amines, or related products
InteractionsBeta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilation induced by albuterol; cardiovascular effects may increase when coadministered with MAOIs, inhaled anesthetics, tricyclic antidepressants, and sympathomimetic agents
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsCaution in hyperthyroidism, diabetes mellitus, or cardiovascular disorders
Drug Name
Theophylline (Theo-Dur, Slo-bid, Theo-24) -- Has a number of physiological effects, including increases in collateral ventilation, respiratory muscle function, mucociliary clearance, and central respiratory drive. Partially acts by inhibiting phosphodiesterase, elevating cellular cyclic AMP levels, or antagonizing adenosine receptors in the bronchi, resulting in relaxation of smooth muscle. However, clinical efficacy is controversial, especially in the acute setting.
Adult DoseTarget concentration: 10 mcg/mL
Dosing = (target concentration - current level) x 0.5 (ideal body weight); alternatively, 1 mg/kg results in approximately 2 mcg/mL increase in serum levels
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity to theophylline, xanthines, or related products; uncontrolled arrhythmias; hyperthyroidism
InteractionsAminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects; effects may be increased by coadministration with allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsCaution in tachyarrhythmias, hyperthyroidism, and patients with compromised cardiac function; do not inject IV solution faster than 25 mg/mm; patients diagnosed with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance
Drug Name
Ipratropium bromide (Atrovent) -- Anticholinergic medication that appears to inhibit vagally mediated reflexes by antagonizing 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. Dose can be combined with a beta-agonist because ipratropium may require 20 min to begin having an effect.
Adult Dose0.5 mg/nebulizer treatment
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsAlbuterol and ipratropium together are more efficacious than either one alone
Drugs with anticholinergic properties (eg, dronabinol) may increase toxicity
Pregnancy B - Usually safe but benefits must outweigh the risks.
PrecautionsNot indicated for initial treatment of acute episodes of bronchospasm; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction
Drug Category: Corticosteroids -- Have been shown to be effective in accelerating recovery from acute COPD exacerbations and are an important anti-inflammatory therapy in asthma. While they may not make a clinical difference in the ED, they have some effect 6-8 h into therapy; therefore, early dosing is critical.
Drug Name
Methylprednisolone (Solu-Medrol, Depo-Medrol) -- Usually given IV in ED for initiation of corticosteroid therapy, although PO should theoretically be equally efficacious.
Adult DoseThe optimal dosage is uncertain
125 mg IV q6h often administered for the first 24-48 h of therapy
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; viral, fungal, or tubercular skin infections
InteractionsClearance may decrease when coadministered with estrogens; when coadministered with digoxin, may increase digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin also may increase metabolism of glucocorticoids; therefore, consider increasing maintenance dose; monitor patients for hypokalemia with concurrent use of diuretics
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsHyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use