19489

8/2/2019 19489

1/13

Respiratory muscle fatigue

Linda Barton, DVMEmergency and Critical Care, The Animal Medical Center, 510 East 62nd Street,

New York, NY 10021, USA

The contribution of respiratory muscle fatigue to the development of ven-

tilatory failure has been the subject of considerable interest and has stimu-

lated much research. Experimental studies in dogs have shown respiratory

muscle fatigue to be a cause of ventilatory failure in both cardiogenic and

septic shock models [1,2]. In clinical conditions resulting in acute or chronic

hypercapnia, respiratory muscle fatigue is believed to occur; however, the

specific role of fatigue has been difficult to prove.

As defined by the National Heart, Lung, and Blood Institutesponsored

Respiratory Muscle Fatigue Workshop Group, respiratory muscle fatigue isa condition in which there is a loss in the capacity for developing force and/

or velocity of a muscle, resulting from muscle activity under load and which

is reversible by rest [3]. Muscle fatigue is distinguished from muscle weak-

ness as a reduction in force generation that is fixed and not reversible by

rest, although muscle weakness may be a predisposition to muscle fatigue.

Muscle fatigue should not be considered in dichotomous terms (present or

absent) but rather as a continuum [4]. Fatigue is a process that begins when-

ever a muscle is subjected to an unsustainable load and may ultimately result

in exhaustion or task failure. Fatigue of the respiratory muscles progressingto task failure results in ventilatory failure. Hypercapnia is the hallmark of

ventilatory failure. Ventilatory failure is characterized by hypoxia and

hypercapnia in contrast to failure of gas exchange, which is characterized

by hypoxia with normo- or hypocapnia. Although discussed as separate

entities, there are interrelations between failure of gas exchange and ventila-

tory failure. Most of the lung diseases that lead to hypoxia also increase the

work of breathing (WOB) and therefore the energy demands of the respira-

tory muscles. Hypoxia itself decreases the amount of energy available to the

respiratory muscles, predisposing them to fatigue [5].

Vet Clin Small Anim 32 (2002) 10591071

E-mail address: [email protected] (L. Barton).

0195-5616/02/$ - see front matter 2002, Elsevier Science (USA). All rights reserved.

PII: S 0 1 9 5 - 5 6 1 6 ( 0 2 ) 0 0 0 3 6 - 0

8/2/2019 19489

2/13

Despite considerable research efforts, the site and mechanism of the

decreased function produced by respiratory muscle fatigue have not been

fully elucidated. Theoretically, fatigue may occur at any point along theextensive chain of command involved in voluntary muscle contrac-

tion, beginning with the brain and ending with the contractile machinery

(brain, spinal cord, nerve, neuromuscular junction, muscle cell membrane,

transverse tubular system, calcium release, actin-myosin activation, and

cross-bridge formation) [4]. Fatigue is generally considered in two broad

categories: failure to generate force because of reduced central motor output

(central fatigue) and failure to generate force because of fatigue either at the

neuromuscular junction or within the muscle machinery (peripheral fatigue)

[4]. Current evidence suggests that the decline in force seen during diaphrag-matic fatigue can be attributed to both central and peripheral fatigue [4,68].

Studies in experimental animals and in healthy human volunteers and

patients suggest that the muscle is the primary site of fatigue and that

changes in central respiratory drive occur to protect the muscle [8,9]. Recent

experimental studies have shown that oxygen-derived free radicals generated

during strenuous contraction can modify respiratory muscle contractile

function and contribute to the development of muscle fatigue [10]. When

inspiratory muscles perform fatiguing work, the central controllers may

reflexively reduce inspiratory time, frequency, the duty cycle (the fractionof the total respiratory cycle duration spent in inspiration), or inspiratory

drive, a strategy that may serve to save energy and avoid exhaustion at the

expense of hypoventilation [9]. Central fatigue may be an inescapable con-

sequence of the imposition of fatiguing loads to breathing and may repre-

sent an important protective mechanism that avoids the adverse effects of

prolonged forceful contraction on the respiratory muscles [6,11].

Physiology of respiratory muscle fatigue

The respiratory muscles, the centers in the central nervous system con-

trolling them, the intervening neural connections, and the structures they

displace (the ribcage and the abdomen) form a pump, which performs the

vital function of ventilating the lungs [12]. Each time a spontaneous breath

is taken, the inspiratory muscles must generate a force sufficient to overcome

the elastic and flow-resistive load imposed by the lungs and chest wall. The

elastic load represents the work performed on the tissue of the lung and

chest wall when a change in volume occurs. The flow-resistive load is the

work performed to overcome airway, tissue, and viscous resistance to gasflow. The ability to take a breath is schematically represented in Figure 1

as a balance between the load imposed on the inspiratory muscles and neu-

romuscular competence. The load imposed on the respiratory muscles

equals the pressure developed by the inspiratory muscles (PI). The maximum

inspiratory pressure (PI, max) is a measure of neuromuscular competence.

Normally, the balance is weighed heavily in favor of neuromuscular

1060 L. Barton / Vet Clin Small Anim 32 (2002) 10591071

8/2/2019 19489

3/13

competence (PI, max). It can be seen that the value of PI/PI, max is determined

by the balance between load and competence. Increased inspiratory load ordecreased neuromuscular competence causes an increase in PI/PI, max. Ven-

tilatory failure results when PI/PI, max reaches a critical value. Table 1 lists

clinical conditions resulting in an increased PI/PI, max.

In health, there are reserves in neuromuscular competence that permit

considerable increases in inspiratory load. For spontaneous ventilation to

continue, however, the inspiratory muscles must be capable of sustaining the

increased load over time. The ability of the respiratory muscles to sustain an

increased load without the appearance of fatigue is called endurance and is

determined by the balance between energy supply and energy demand [12].Figure 2 illustrates the variables affecting respiratory muscle endurance.

Energy supplies depend on the inspiratory muscle blood flow, the concentra-

tions of oxygen and blood substrate concentrations, the muscles ability to

extract and utilize energy sources, and the muscles energy stores. Energy

demands increase proportionally with the mean tidal pressure developed

by the inspiratory muscles (PI), which is expressed as a fraction of the max-

imal inspiratory pressure (PI/PI, max), the minute ventilation (V0

E), the

inspiratory duty cycle (tI/ttot), and the mean inspiratory flow rate (VT/tI).

Energy demands are inversely related to the efficiency of the muscles[5,9,12]. Under normal conditions, energy supplies are adequate to meet

demands and a large recruitable reserve exists. Fatigue develops when the

mean rate of energy demands exceeds the mean rate of energy.

It can be seen that the value of PI/PI, max is determined by the balance

between inspiratory muscle load and neuromuscular competence. PI/PI, maxis also one of the determinants of respiratory muscle energy demands;

Fig. 1. The ability to take a spontaneous breath is determined by the balance between the load

imposed on the respiratory muscles (PI) and the neuromuscular competence of the ventilatory

pump (PI/PI, max).

1061L. Barton / Vet Clin Small Anim 32 (2002) 10591071

8/2/2019 19489

4/13

therefore, the two balances (between load and competence and energy sup-

ply and demand) are linked. In rat studies, PI/PI, max has been directly

related to diaphragm endurance time. Roussos et al [13] demonstrated that

the critical value of PI/PI, max that could be generated indefinitely at func-tional residual capacity was around 0.06. Greater values of PI/PI, max were

inversely related to the endurance time in a curvilinear fashion.

Factors predisposing to respiratory muscle fatigue

From the previous discussion, it can be seen that fatigue of respiratory

muscles can occur when there is an unfavorable balance between the factors

affecting energy supply, energy demand, and neuromuscular competence.

Energy supply

Important factors affecting the supply of energy to the respiratory

muscles are the, oxygen concentration of the blood, cardiac output, and

blood substrate concentration (ie, glucose, free fatty acids). Arterial oxygen

concentration is decreased with anemia, decreased hemoglobin oxygen

Table 1

Clinical conditions causing an increase in PI/PI, max

Increased load (PI) Decreased neuromuscular competence (PI, max)Increased restrictive load Decreased central drive

Bronchospasm Drug overdose

Airway edema/increased secretions Brain stem lesion

Upper airway obstruction Hypothyroidism

Ventilatory circuit resistance

(ventilated patients)

Malnutrition

Metabolic alkalosis

Endotracheal tube kinking

(ventilated patients)

Increased lung elastic load Muscle weakness

Hyperinflation

(autopositive end-expiratory pressure)

Electrolyte derangement

Malnutrition

Alveolar edema Myopathy

Infection Hyperinflation

Atelectasis Corticosteroids

Interstitial inflammation/edema Disuse atrophy

Lung tumor Sepsis

Increased chest wall elastic load Impaired nerve/neuromuscular transmission

Pleural effusion Phrenic nerve injury

Pneumothorax Spinal cord lesion

Flail chest Neuromuscular blockers

Tumor Myasthenia gravis

Obesity Aminoglycosides

Ascites Botulism

Abdominal distention


8/2/2019 19489

5/13

binding capacity, and hypoxemia. In addition to adequate oxygen delivery,

the muscle must be able to extract and utilize energy from the blood. In sep-

sis, increases in respiratory muscle oxygen consumption out of proportion to

load suggest that the processes of oxygenation and phosphorylation are

uncoupled [12,14]. Blood flow to muscles may be decreased in low cardiac

output states. In experimental models of cardiogenic and septic shock, it has

been shown that blood flow to the inspiratory muscles remained high, rep-

resenting a substantial percentage of cardiac output. The amount of bloodflow was insufficient, however, and led to fatigue of the respiratory muscles

and inability to maintain alveolar ventilation [1,2,12]. Blood flow to muscles

can also be decreased during strenuous inspiratory efforts. Forceful muscle

contractions cause compression of intramuscular vessels, limiting nutrient

blood flow. Because unimpeded flow blood occurs only during expiration,

increases in the duty cycle also decrease blood flow to the muscles. In severe

Fig. 2. Respiratory muscles ultimately fatigue if the energy demands exceed the energy supplied

to the muscles. PI/PI, max inspiratory pressure/maximum inspiratory pressure; _VVE minute

ventilation; tI/ttotduty cycle (fraction of inspiration to total breathing cycle duration);

VT/tI

mean inspiratory flow (tidal volume/inspiratory time).


8/2/2019 19489

6/13

asthma, inspiratory muscles may continue to contract during expiration,

further limiting blood flow and increasing the vulnerability of the respiratory

muscles to fatigue [9]. Malnutrition and catabolic states can cause depletionof glycogen and other energy stores, predisposing to muscle fatigue.

Energy demands

The clinical conditions causing increased inspiratory load are listed in

Table 1. Intrinsic positive end-expiratory pressure (PEEPi) refers to positive

pressure in the alveoli at the end of expiration. PEEPi develops from airflow

obstruction or decreased elastic recoil of the lung and has been detected in

patients with chronic obstructive pulmonary disease (COPD), cardiogenic

pulmonary edema, chest trauma, and pneumonia [12]. PEEPi increases the

lung elastic load, because the inspiratory muscles have to develop a pressure

equal to the level of PEEPi before airflow can begin.

Energy demands increase proportionally with increases in minute ventila-

tion. For PaCO2 to remain at its normal value, minute ventilation must

increase whenever there is an increase in carbon dioxide production or an

increase in dead space ventilation. Carbon dioxide production may increase

as a result of the following:

1. Fever or sepsis: carbon dioxide production increases during hyperther-mia by approximately 9% to 14% for each degree Centigrade rise in tem-

perature.

2. Shivering: an increase in either physiologic or pathologic (ie, seizures)

muscle tone increases the metabolism of the muscles and thus carbon

dioxide production.

3. Agitation: carbon dioxide production is increased secondary to in-

creased muscle activity.

4. Severe burns or trauma: being catabolic states, these conditions elevate

carbon dioxide production.5. Hyperalimentation: intravenous hyperalimentation in excess of caloric

requirement increases carbon dioxide production [12,15].

It has previously been suggested that diets high in carbohydrates were

harmful to patients with ventilatory compromise. To elucidate the relative

importance of excess carbohydrates versus excess total calories in carbon

dioxide production, Talpers et al [16] compared three isocaloric regimens

containing 40%, 60%, and 75% carbohydrates and found no difference in the

amount of carbon dioxide produced. In contrast, when carbohydrates wereheld constant but total calories were increased, carbon dioxide production

increased from 181 mL/min1 when calories were equivalent to the calcu-

lated resting energy requirement (REE) to 211 mL/min1 at 1.5 REE and

244 mL/min1 at 2.0 REE [12].

Physiologic dead space is increased in virtually all the diverse processes

that affect the lung parenchyma and the distribution of airflow. Alveolar dead


8/2/2019 19489

7/13

space increases if lung perfusion is reduced. Decreased perfusion is seen sec-

ondary to pulmonary embolism and hypovolemia. During positive-pressure

ventilation, there is alveolar wall distention and compression of the capilla-ries of the well-ventilated alveoli, causing increased dead space [12].

Efficiency is defined as the ratio of mechanical work to the oxygen cost of

breathing. Therefore, energy demands increase when muscle efficiency is

decreased. Hyperinflation reduces the efficiency of the respiratory muscles

[5,9,12]. As lung volume increases, shortening of the inspiratory muscles and

alterations in their geometry require greater excitation and energy consump-

tion to perform a given amount of work. Like other skeletal muscles, respi-

ratory muscles obey the length-tension relation. At any given level of

activation, changes in muscle fiber length alter active and passive tension,modifying actin-myosin interaction. At a specific fiber length (Lo), active

tension is maximal, whereas it declines below and above the Lo [12,17].

Respiratory muscle length depends largely on lung volume and, to a lesser

extent, on thoracoabdominal configuration. Animal experiments have shown

that the Lo for inspiratory muscles (diaphragm and intercostals) is near

residual volume [12]. Respiratory muscle efficiency is also reduced when

the inspiratory load is increased [5].

Decreased neuromuscular competence

Decreased respiratory drive or altered neural transmission may cause a

decrease in PI, max. The most common cause of decreased competence in crit-

ically ill patients is muscle weakness. Mechanically ventilated patients may

develop muscle weakness secondary to disuse atrophy. Electrolyte imbalances

(hypocalcemia, hypokalemia, hypophosphatemia, and both hypo- and hyper-

magnesemia) can adversely affect muscle strength. Molloy et al [17] reported

an improvement in all measured parameters of respiratory muscle power

when 17 hypomagnesemic patients were treated intravenously with magne-

sium. Administration of corticosteroids has been shown to cause respiratory

muscle weakness. Decramer et al [19] reported a significant relation between

maximal inspiratory pressure measured 10 days after admission and the aver-

age daily dose of corticosteroid during the previous 6 months in patients with

an exacerbation of COPD and asthma. Patients with no underlying pulmo-

nary disease developed reversible inspiratory muscle weakness as a result of

high-dose steroids administered over several weeks [20]. Fluorinated steroids,

such as triamcinolone and dexamethasone, lead to more marked myopathy

than nonfluorinated steroids, such as hydrocortisone, prednisone, and corti-

sone acetate [15]. Muscle strength is also affected by malnutrition.

Detection of respiratory muscle fatigue

The diagnosis of fatigue requires demonstration of a decrease in force

generation. Such measurements can be made in experimental settings but


8/2/2019 19489

8/13

have proven more difficult in patient populations. In the clinical setting, it is

difficult to control other variables (eg, changes in lung volume, changes in

chest wall geometry, patient cooperation) that may affect the result[4,5,17]. Bedside measurement is also difficult because of lack of baseline

measurement before fatigue.

Analysis of the electromyographic (EMG) power spectrum has been used

to detect inspiratory muscle fatigue. It has been shown that during fatigue,

the power of the low-frequency components of the EMG power spectrum

increases, whereas the power of the high-frequency components decreases.

The shift in the power spectrum occurs before the loss of force generation,

making it a useful test to monitor for the development of fatigue. Use of this

analysis is limited, however, because measurement of the power spectrum at asingle point in time is inadequate to detect fatigue; the power shift must be

observed as the muscle passes from the rested to the fatigued state. The tech-

nique has been used to detect the development of fatigue during weaning

from mechanical ventilation [4,5,17,18,21]. Recently, some doubt has been

cast on the validity of this technique. The measurement of electric activity

of the inspiratory muscles can be influenced by changes in the spatial relations

between the recording electrodes and the muscle. Secondly, the cellular mech-

anisms responsible for the shifts in the power spectrum are unknown [17].

The rate of relaxation of the diaphragm has been used to detect musclefatigue. An early physiologic event in the progress of a fatiguing contraction

is the slowing of the muscle relaxation rate. Maximum relaxation rate

(MRR) also requires serial measurements for detection of fatigue. The wide

range of normal values for MRR makes it difficult to obtain useful informa-

tion from a single measurement [4]. Goldstone et al [22] measured MRR in a

group of intubated patients before and during weaning. Serial measure-

ments of MRR remained unchanged in patients who weaned successfully

and slowed in patients failing to wean.

A sequence of changes in breathing pattern suggestive of respiratorymuscle fatigue has been described. First, there is an early stage of rapid shal-

low breathing. There is then an inward displacement of the abdomen accom-

panied by a decrease in abdominal pressure during inspiration (abdominal

paradox) and uncoordinated chest wall movements characterized by altera-

tion between predominantly abdominal and ribcage displacements during

inspiration (respiratory alternans). These changes are generally seen before

increases in carbon dioxide. Subjects become bradycardic as ventilatory fail-

ure develops [9,13,21]. Cohen et al [21] compared changes in the EMG

power spectrum to observed physical examination parameters in 12 patientswho experienced difficulty during weaning. Seven patients developed

changes in the EMG power spectrum indicative of fatigue. Physical exami-

nation changes were noted in these patients, including increased respiratory

rate (6/7), abdominal paradox (6/7), and respiratory alternans (4/7). In all

instances, the shift in the EMG power spectrum was seen in advance of the

changes in respiratory pattern. Changes in the respiratory pattern were not


8/2/2019 19489

9/13

8/2/2019 19489

10/13

unloaded, partially loaded, or fully loaded [25]. During controlled ventila-

tion, no inspiratory effort is made by the patient; the ventilator provides all

the necessary work. Controlled ventilation causes respiratory muscles to beunloaded, predisposing to atrophy. Muscles that are used most often, such

as the inspiratory muscles, atrophy the fastest [4]. In contrast, increased

muscle loading leading to muscle fatigue can occur from insufficient ventila-

tory support. Increased WOB may occur with ventilatory modes tradition-

ally thought to provide respiratory muscle rest, such as assist-control (AC)

and synchronized intermittent mandatory ventilation (SIMV) [3,25,27,29].

Studies have shown that substantial patient work is performed during SIMV

and AC [3,29]. In one study, patient work was 33% to 50% of the work

required to passively inflate the chest and, on average, accounted for 63%of the total work during spontaneous breathing [29]. With either fatigue

or atrophy, the respiratory muscles are weak and incapable of generat-

ing sufficient force to maintain alveolar ventilation and allow weaning [26].

Civetta [30] has suggested the term nosocomial respiratory failure or iatro-

genic ventilator dependency to describe the inappropriate prolongation of

ventilatory support caused by either respiratory muscle atrophy or fatigue.

Newer modes of ventilation, such as pressure support, allow partial loading

of respiratory muscles to prevent nosocomial respiratory failure. Brochard

et al [26] reported that EMG power spectrum changes consistent with dia-phragmatic fatigue in patients failing to wean could be reversed with the

addition of 15 cm H2O of pressure support.

With the recent availability of bedside monitoring of WOB, there is grow-

ing interest in the estimation of WOB in the management of mechanically

ventilated patients, especially during weaning. It is recommended that ven-

tilatory support be titrated to maintain normal physiologic work [25,26,28].

Ventilatory therapy guided by WOB estimates has been advocated to

prevent muscle fatigue and allow for more rapid weaning, resulting in a

reduction in length of stay in the intensive care unit and hospital costs[25,26]. WOB measurements have been used to guide weaning [11,31]. In

each of these studies, WOB was measured if patients failed a 20-minute

spontaneous breathing trial. If the physiologic WOB was not excessive, the

patient was extubated despite tachypnea. In the study by Kirton et al [11], 20

of 21 patients were successfully weaned. In the study by DeHaven et al [31],

97 of 105 patients were successfully weaned. A weaning protocol based on

WOB estimation was shown to result in more aggressive weaning [32]. On

average, patients were weaned 1.68 days faster on the WOB protocol than

patients weaned on a conventional protocol.

Treatment

Energy supply, energy demand, and neuromuscular competence are

closely linked, and imbalances in these parameters can lead to respiratory

muscle fatigue. Therefore, it is rational to direct therapeutic efforts toward


8/2/2019 19489

11/13

increasing energy supply to the respiratory muscles, minimizing energy

demands, and maximizing neuromuscular competence by improving con-

tractility and optimizing respiratory drive.

Increasing energy supply

Energy supply to the respiratory muscles can be increased by improving

cardiac output. Decreases in hemoglobin concentration or PaO2 cause a

reduction in the oxygen content of arterial blood and therefore decreased

oxygen delivery. Anemia or hypoxia should be identified and corrected to

improve oxygen delivery to the respiratory muscles.

Minimizing energy demand

Therapy directed at reducing airway resistance by bronchodilation or

increasing pulmonary compliance by treating pulmonary edema reduces the

load and the energy demands of the inspiratory muscles.

Respiratory muscle energy demands can be substantially decreased by

mechanical ventilation. Controlled ventilation to provide total rest is advo-

cated for fatigued muscles. A 24-hour period of complete rest has been

advocated as a reasonable time to allow muscle recovery from fatigue[25]. Mechanical ventilation is also recommended in circumstances where

cardiac output is inadequate. In conditions like cardiogenic shock, when

total body oxygen delivery is reduced, delivery of blood to the working res-

piratory muscles may steal oxygen from other tissues, predisposing them

to dysfunction [5,9,12,33]. Viires et al [33] have demonstrated this stealing

effect in experimental models of cardiogenic shock. They have shown that

the respiratory muscles of spontaneously breathing dogs with a low cardiac

output produced by pericardial tamponade received more than 20% of the

cardiac output compared with 3% when the animals were paralyzed andventilated. The large fraction of the cardiac output taken up by the respira-

tory muscles in the spontaneously breathing animals resulted in reduced

blood flow to the brain, liver, and other skeletal muscles compared with the

mechanically ventilated animals with a similar reduction in cardiac output.

Maximizing neuromuscular competence

Muscle strength is an important component of neuromuscular com-

petence. Treatable or avoidable causes of muscle weakness, including hy-percapnia, acidosis, hypocalcemia, hypokalemia, hypomagnesemia, and

hypophosphatemia, should not be ignored. Inadequate nutrition adversely

affects muscle strength. The strength of the ventilatory pump can be im-

proved with nutritional repletion.

Attention has been given to the use of pharmacologic agents to improve

the contractility and endurance of the respiratory muscles. A number of


8/2/2019 19489

12/13

drugs, including xanthines, glycosides, catecholamines, and phosphodiester-

ase inhibitors, have been investigated [4,5,9,34]. Theophylline has been

shown to have a positive inotropic effect on respiratory muscles at therapeu-tic doses. The effects of theophylline seem to be greater on fatigued muscle

than on rested muscle. The mechanism of action is not clear, but it is thought

to facilitate the influx of calcium through the slow channels and by activation

of a calcium-induced calcium release from the sarcoplasmic reticulum [4].

Specific training of the respiratory muscles has been shown to enhance

strength and endurance in human patients with chronically increased

inspiratory loads; however, this requires a level of patient cooperation not

available with veterinary patients.

References

[1] Aubier M, Trippenbach T, Roussos C. Respiratory muscle fatigue during cardiogenic

shock. J Appl Physiol 1981;51:499508.

[2] Hussain SN, Magder AC, Roussos C. Respiratory muscle fatigue: a cause of ventilatory

failure in septic shock. J Appl Physiol 1985;58:203340.

[3] NHLBI Workshop on Respiratory Muscle Fatigue. Report of the Respiratory Muscle

Fatigue Workshop Group. Am Rev Respir Dis 1990;142:47480.

[4] Roussos C, Zakynthinos S. Fatigue of the respiratory muscles. Intensive Care Med1996;22:13455.

[5] Roussos C, Macklem PT. The respiratory muscles. N Engl J Med 1982;307:78697.

[6] DeTroyer A. Respiratory muscle function. In: Shoemaker WC, Ayres SM, Grenvik A, et al,

editors. Textbook of critical care. 4th edition. Philadelphia: WB Saunders; 2000. p. 117284.

[7] Gandevia SC, Allen GM, Butler JE, et al. Human respiratory muscles: sensations, reflexes

and fatiguability. Clin Exp Pharmacol Physiol 1998;25:75763.

[8] McKenzie DK, Bellemare F. Respiratory muscle fatigue. Adv Exp Med Biol 1995;384:

40114.

[9] Roussos C, Macklem PT. Clinical implications of respiratory muscle fatigue. In: Fishman

AP, editor. Pulmonary disease and disorders. 2nd edition. New York: McGraw-Hill; 1988.

p. 227586.[10] Supinski G. Free radical induced respiratory muscle dysfunction. Mol Cell Biochem 1998;

179:12534.

[11] Kirton OC, DeHaven B, Morgan JP, et al. Elevated imposed work of breathing

masquerading as ventilator weaning intolerance. Chest 1995;108:10215.

[12] Vassilakopoulos T, Zakynthinos S, Roussos C. Respiratory muscles and weaning failure.

Eur Respir J 1996;9:2383400.

[13] Roussos C, Fixley M, Gross D, et al. Fatigue of inspiratory muscles and their synergic

behaviour. J Appl Physiol 1979;46:897904.

[14] Hussain SN. Respiratory muscle dysfunction in sepsis. Mol Cell Biochem 1998;179:12534.

[15] Reid WD, MacGowan NA. Respiratory muscle injury in animal models and humans. Mol

Cell Biochem 1998;179:6380.[16] Talpers SS, Romberger DJ, Bunce SB, et al. Nutritionally associated increased carbon

dioxide production (excess total calories vs high proportion of carbohydrate calories).

Chest 1992;102:5515.

[17] Molloy DW, Dhingra S, Solven F, et al. Hypomagnesemia and respiratory muscle power.

Am Rev Respir Dis 1984;129:4978.

[18] Marini JJ, Rodriguez RM, Lamb V. The inspiratory workload of patient initiated

mechanical ventilation. Am Rev Respir Dis 1986;134:9029.


8/2/2019 19489

13/13

[19] Decramer M, Lacquet LM, Fagard R, et al. Corticosteroids contribute to muscle weakness

in chronic airflow obstruction. Am J Respir Crit Care Med 1994;150:116.

[20] Weiner P, Azgad Y, Weiner M. Inspiratory muscle training during treatment with cor-

ticosteroids in humans. Chest 1995;107:10414.

[21] Cohen CA, Zagelbaum G, Gross D, et al. Clinical manifestations of inspiratory muscle

fatigue. Am J Med 1982;73:30816.

[22] Goldstone JC, Green M, Moxham J. Maximum relaxation rate of the diaphragm during

weaning from mechanical ventilation. Thorax 1994;49:5460.

[23] Tobin MJ, Guenther SM, Perez W, et al. Konno-Mead analysis of ribcage-abdominal

motion during successful and unsuccessful trials of weaning from mechanical ventilation.

Am Rev Respir Dis 1987;135:13208.

[24] Tobin MJ, Guenther SM, Perez W, et al. Does rib cage-abdominal paradox signify

respiratory muscle fatigue. Am J Med 1982;73:30816.

[25] French CJ. Work of breathing measurements in the critically ill patient. Anaesth Intensive

Care 1999;27:56173.

[26] Brochard L, Harf A, Lorino H, et al. Inspiratory pressure support prevents diaphragmatic

fatigue during weaning from mechanical ventilation. Am Rev Respir Dis 1989;139:51321.

[27] Tobin MJ, Laghi F, Jubran A. Respiratory muscle dysfunction in mechanically-ventilated

patients. Mol Cell Biochem 1998;179:8798.

[28] Banner MJ. Respiratory muscle loading and the work of breathing. J Cardiothor Vasc

Anesth 1995;9:192204.

[29] Marini JJ, Capps JS, Culver BH. The inspiratory work of breathing during assisted

mechanical ventilation. Chest 1985;87:6128.

[30] Civetta JM. Nosocomial respiratory failure or iatrogenic ventilator dependency. Crit Care

Med 1993;21:1713.[31] DeHaven CB, Kirton OC, Morgan JP, et al. Breathing measurements reduced false-

negative classification of tachypneic preextubation trial failures. Crit Care Med 1996;24:

97680.

[32] Gluck EH, Barkoviak MJ, Balk RA, et al. Medical effectiveness of esophageal balloon

pressure manometry in weaning patients from mechanical ventilation. Crit Care Med

1995;23:5049.

[33] Viires N, Sillye G, Aubier M, et al. Regional blood flow distribution in dogs during induced

hypotension and low cardiac output: spontaneous breathing versus artificial ventilation.

J Clin Invest 1983;72:93547.

[34] Fujii Y, Hoshi T, Toyooka H. Colforsin daropate improves contractility in fatigued canine

diaphragm. Anesth Analg 2001;92:7626.


Documents

19489