Ventilatory Workload or Demand

Patients who need mechanical ventilation often have a ventilatory workload or demand that exceeds their ventilatory capacity. This is the most common cause of ventilator dependence.1,2 The term ventilatory workload refers to the amount of work that the respiratory muscles are asked to perform to provide an appropriate level of ventilation. A patient’s total ventilatory workload is primarily determined by the following: (1) the level of ventilation needed; (2) the compliance of the lungs and thorax; (3) the resistance to gas flow through the airways, and (4) any imposed work of breathing (WOB_i) due to mechanical factors.^1,7

The level of ventilation required is determined by the following: (1) the metabolic rate; (2) the central nervous system (CNS) drive; and (3) the ventilatory dead space. Common causes of an increased demand for ventilation include increased carbon dioxide production (i.e., fever, shivering, agitation, trauma, or sepsis) and increased dead space (i.e., pulmonary emboli or chronic obstructive pulmonary disease [COPD]). Other common causes of increased ventilatory demand include metabolic acidosis, severe hypoxemia, pain, and anxiety.

Compliance is determined by the elastic nature of the lung–thorax system. Resistance is largely related to the nature of the conducting airways. Common causes of decreased lung compliance include atelectasis, pneumonia, pulmonary edema, acute lung injury, and acute respiratory distress syndrome. Thoracic compliance may be reduced because of obesity, ascites, or abdominal distention. Airway resistance increases with bronchospasm, excessive secretions, and mucosal edema.

Mechanical factors that can increase the work of breathing include artificial airways (i.e., endotracheal and tracheotomy tubes), partial obstruction of the airway, ventilator circuits, demand flow systems, auto-PEEP, and inappropriate ventilator flow and sensitivity settings. Factors that may increase ventilatory workload are summarized in Box 47-1.

Ventilatory Capacity

Ventilatory capacity is determined by CNS drive, ventilatory muscle strength, and ventilatory muscle endurance.¹⁸ Most patients who are being withdrawn from ventilatory support have a normal or an increased drive to breathe. Patients with neuromuscular disorders and those who are receiving sedatives, narcotics, or neuromuscular blocking agents may have a reduced drive to breathe or impaired neuromuscular transmission. Patients with metabolic alkalosis, hypothyroidism, and sleep deprivation also may have reduced ventilatory drive. Box 47-2 summarizes the factors that may reduce ventilatory drive.

Muscle strength is influenced by age, sex, muscle bulk, and overall health. Malnutrition, starvation, and electrolyte imbalances (especially involving calcium, magnesium, potassium, and phosphate) can lead to ventilatory muscle weakness.18,19 Critical illness myopathy, critical illness polyneuropathy, and the prolonged use of neuromuscular blocking agents are major causes of the development of ventilatory muscle weakness in the intensive care unit (ICU).²⁰ Controlled ventilation for prolonged periods can result in ventilatory muscle discoordination and atrophy.¹⁸ Ventilatory muscle endurance is a function of energy supply versus demand. Energy supply is related to nutrition, perfusion, and cell use, whereas demand is related to the amount of work performed and is a function of minute ventilation, compliance, and resistance. Figure 47-1 summarizes the relationship between ventilatory demands and capabilities.

Global Criteria for Discontinuing Ventilatory Support

Success with the discontinuation of ventilatory support is related to the patient’s condition in four main areas1,2,7:

Simply put, when ventilatory workload or demand exceeds ventilatory capacity, successful ventilator discontinuation is unlikely.1,2 Excessive ventilatory workload may lead to ventilatory muscle fatigue. When the ventilatory muscles fatigue, they must be rested for at least 24 hours to recover.^3,4,19 Ventilatory workload increases with decreased compliance, increased airway resistance, or an increased level of ventilation. Ventilatory capacity can be reduced by ventilatory muscle fatigue and by a loss of muscle strength and endurance.

Other factors that may contribute to ventilator dependence include inadequate arterial oxygenation, poor tissue oxygen delivery, myocardial ischemia, arrhythmias, low cardiac output, and cardiovascular instability.7,16 Neurologic problems that may contribute to ventilator dependence include decreased central drive to breathe and impaired peripheral nerve transmission.³ Psychologic issues that may contribute to ventilatory dependence include the fear of removal of the life support system, anxiety, stress, depression, and sleep deprivation.³ Box 47-3 summarizes the major factors that contribute to ventilator dependence.

The Most Important Criterion

The single most important criterion to consider when evaluating a patient for ventilator discontinuation or weaning is whether there has been significant alleviation or reversal of the disease state or condition that necessitated use of the ventilator in the first place.3,7,14 The clinician should determine whether the patient’s condition is improving, whether the initial reason for providing ventilatory support is improved or resolved, and whether the patient’s clinical condition is stable. The following specific questions for patient evaluation have been suggested³:

If the patient’s condition is improving, if the alleviation or reversal of the precipitating disease state or condition has occurred, if the patient is capable of spontaneous breathing, and if the oxygenation status and hemodynamic values are stable, then a formal evaluation for ventilator discontinuation should be performed.³

Weaning Indices

Mechanical ventilation is hazardous, and unnecessary delays in ventilator discontinuation increase the associated complication rate.3,4 Unfortunately, premature ventilator discontinuation may also cause serious problems, including difficulty with reestablishing the artificial airway and serious compromise of the patient’s clinical status.^3,4 Clinical judgment has been found to be a poor guide to determining whether a patient is ready for ventilator discontinuation, and more specific indicators have been sought.⁴ Ideally, specific indicators or weaning indices would clearly show whether a patient is ready to have the ventilator removed and would help to avoid inappropriate ventilator discontinuation. Unfortunately, none of the current weaning indices are capable of predicting readiness for ventilator discontinuance with a high level of accuracy.

Traditional discontinuation indices include the PaO₂/FiO₂ ratio, the alveolar-to-arterial partial pressure of oxygen difference [P(A–a)O₂], the maximum inspiratory pressure (MIP), the vital capacity (VC), the spontaneous minute ventilation (V_Esp), and the maximum voluntary ventilation (MVV).5,21 Newer indices include the rapid, shallow breathing index (f/V_t), airway occlusion pressure (P_0.1), and measures of WOB.^6–8 Although all of these values can be useful, there are enormous discrepancies in the literature regarding their accuracy with regard to the prediction of “weanability.”^3,6,7 With respect to the more traditional discontinuation indices, vital capacity and MIP can be highly variable, whereas minute ventilation, respiratory rate (f), and f/V_t tend to be more reliable.²² However, these measures may not correlate well with discontinuation success among all patients and especially among those receiving long-term ventilatory support, the elderly, and those with major pulmonary abnormalities.^5,18,23

A comprehensive evidence-based review identified a possible role for 66 specific measurements as predictors of weaning success.⁶ Of these, eight values were found to be the most useful for the prediction of successful ventilator discontinuation.^3,6 Useful predictive measures included spontaneous respiratory rate, spontaneous tidal volume, f/V_t, minute ventilation, MIP, P_0.1, P_0.1/MIP, and a combined index called the CROP score that included compliance, rate, oxygenation, and MIP.^3,6 Unfortunately, these measures all have limitations and relatively high false-positive predictions in specific settings.

It is doubtful that a single index will be found that can be used for consistent discrimination between discontinuation success and failure.⁷ Moreover, none of these traditional indicators alone has proved useful for the prediction of improvements in patient outcome or in the selection of a particular discontinuation method.^7,10 The likely explanation for this failure to identify any consistently powerful discontinuation predictor is that patients’ conditions vary greatly and, for research purposes, clinicians already fully consider information from predictors when choosing patients for trials of the reduction or discontinuation of ventilatory support.^10,23

Notwithstanding these limitations, the measurement of discontinuation indices in the difficult-to-wean patient may provide guidance with regard to the reasons that patients fail discontinuation trials. Many find it useful to trend these data on a daily basis for those patients who require lengthy weaning times.¹⁵ Specific values for respiratory indices that are used to predict the successful discontinuation of ventilatory support are found in Table 47-1.

TABLE 47-1

Indices That Are Used to Predict the Success of Weaning and Ventilator Discontinuation

Measurement	Criterion
Oxygenation
FiO2	≤0.40 to 0.50
PEEP (cm H2O)	≤5 to 8
PaO2 (mm Hg)	≥60
SaO2 (%)	≥90
SvO2 (%)	≥60
PaO2/PAO2 ratio	≥0.35
PaO2/FiO2 ratio	>150 to 200
P(A-a)O2 (mm Hg)	<350
(% shunt)	<15% to 20%
No lactic acidosis, adequate , blood pressure
Ventilation
PaCO2 (mm Hg)	<50
pH	≥7.35
Ventilatory Mechanics
Respiratory rate (f) (breaths/min)	12 to 30
Tidal volume (VT) (ml/kg)	>5
Vital capacity (VC) (ml/kg)	>10 to 15
Static compliance (ml/cm H2O)	>25
f/VT	<105
Respiratory Muscle Strength
Maximum inspiratory force (MIF) (cm H2O)	<−20 to −30
Ventilatory Drive (Demand)
Minute ventilation () for
Normal PCO2 (L/min)	<10
VDS/VT	<0.55 to 0.60
P0.1 (cm H2O)	<6
P0.1/MIP	<0.30
Work of Breathing
Spontaneous work of breathing	<1.6 kg·m/min (<0.14 kg·m/L)
Pressure–time index	<0.15 to 0.18
Ventilatory Reserve
Maximum voluntary ventilation (MVV) (L/min)	>20; more than twice the

Data from MacIntyre NR, Cook DJ, Ely EW, et al: Evidence-based guidelines for weaning and discontinuing ventilator support: a collective task force facilitated by the American College of Chest Physicians, the American Association for Respiratory Care, and the American College of Critical Care Medicine. Chest 120:375S–395S, 2001; AHRQ publication no. 01-E010, Rockville, MD, 2000, Agency for Healthcare Research and Quality; American College of Chest Physicians: Chest 104:1833, 1993; Burns SM et al: Am J Crit Care 4:4, 1995; Sharar S: Resp Care 40:239, 1995; Bassili HR, Deitel M: JPEN J Parenter Enteral Nutr 5:161, 1981.

Ventilation

Increased thoracic cage movement during spontaneous breathing and asynchronous chest-wall-to-diaphragm movement are related to an increased workload that may lead to ventilatory muscle fatigue and failure.¹⁹ Tachypnea (i.e., more than 30 to 35 breaths/min) is a sensitive marker of respiratory distress, but it can prolong intubation if it is used as an exclusive criterion.²⁵ Irregular spontaneous breathing or periods of apnea indicate that the patient is at risk for weaning failure. Asynchronous and rapid, shallow breathing patterns—although not definitive—suggest respiratory decompensation.¹⁹

The evaluation of patients for the presence of palpable scalene muscle use during inspiration, an irregular ventilatory pattern, palpable abdominal muscle tensing during expiration, and the inability to alter the ventilatory pattern on command can be helpful for the assessment of the potential for prolonged spontaneous ventilation. Patients with none of these signs have a 90% chance of success.²⁶ Patients with one or two of these signs usually need continued support. The presence of three or more of these signs can mean that the patient’s condition is unstable and that the patient has a poor prognosis for ventilator removal.

P_0.1 is the inspiratory pressure that is measured 100 milliseconds after airway occlusion.²¹ The P_0.1 is effort independent, and it correlates well with central respiratory drive.¹⁹ Ventilator-dependent patients with COPD who have a P_0.1 of more than 6 cm H₂O tend to be difficult to wean.²¹

The f/V_t is the ratio of spontaneous breathing frequency (breaths/min) to tidal volume (liters), and it has been found to be a good predictor of discontinuation success for the care of many patients who need mechanical ventilation.4,6,23 The f/V_t has less predictive power for the care of patients who need ventilatory support for longer than 8 days, and it may be less useful for predicting discontinuation success among elderly patients.^8,23,27 Adjusting the threshold value for f/V_t to 130 or less measured at 3 hours was very effective for predicting discontinuation success among patients 70 years old and older. Despite these limitations, an f/V_t of less than 105 can be an accurate and early predictor of weaning outcome, and an f/V_t of 80 is associated with an almost 95% probability of successful discontinuation.^4,23 The ratio must be calculated during 1 minute of unsupported spontaneous breathing, and the addition of pressure support significantly reduces the predictive value of the ratio.⁴

The P_0.1/MIP ratio has been found to be a good early predictor of discontinuation success,3,19 and it may be more useful than the MIP by itself. The f/V_t also has been found to be a better predictor of discontinuation success than the MIP alone.^2,3 However, even with f/V_t of less than 105, as many as 20% of patients have false-positive results (i.e., they cannot be discontinued from ventilation despite a favorable index) as a result of unpredictable factors such as congestive heart failure, aspiration, or the development of a new pulmonary lesion.²⁸ However, some patients can be successfully discontinued from ventilatory support despite poor f/V_t values.²⁹

WOB would seem to be an excellent way to gauge spontaneous ventilatory workload. Successful weaning has been found to be less likely among patients with spontaneous WOB levels of more than 1.6 kg/m/min (16 J/min) or 0.14 kg/m/L (1.4 J/L).⁵ However, WOB may not be predictive of weaning success for specific patients.⁷ This may be because WOB does not take into account ventilatory muscle capacity or fatigue. Consequently, WOB may be less accurate than other conventional discontinuation indices, and it is very difficult to measure at the bedside.³⁰

Oxygen cost of breathing (OCB) is the difference between oxygen consumption during spontaneous breathing and oxygen consumption during apnea (i.e., during full ventilatory support), which is determined as follows:

OCB=VO2sp−VO2(controlled ventilation)

After the OCB has been estimated, the relative proportion of oxygen consumed by the respiratory muscles as compared with the body as a whole can be calculated as follows:

%VO2(Resp)=(OCB/VO2sp)×100

Both OCB and %VO₂ have been correlated with the number of days required to wean patients.¹⁹ Patients with an OCB of 15% or less of the total VO₂ may be more likely to achieve discontinuation success. In one study, OCB was a better predictor of discontinuation success than was f/V_t.³¹

Pressure–time product (i.e., the area under the inspiratory pressure–time curve) and pressure–time index (PTI) may be the best measures of ventilatory workload for the care of patients who are receiving mechanical support.¹ The PTI can be calculated as follows:

PTI=(Mean inspiratory pressure/MIP)×Ti/Ttot

where MIP is maximum inspiratory pressure, T_i is the inspiratory time in seconds, and T_tot is the total respiratory cycle. The T_tot can be calculated by dividing 60 by the respiratory rate (f) (i.e., 60/f). A PTI of more than 0.15 to 0.18 has been associated with diaphragmatic fatigue,³² and a PTI of more than 0.15 cannot be sustained indefinitely.¹ There is currently no well accepted and reliable way to measure ventilatory muscle fatigue for patients who are receiving mechanical ventilation.⁵

Oxygenation

Poor oxygenation status is associated with weaning failure.3,7 Arterial blood gas (ABG) analysis, pulse oximetry, and continuous mixed venous oximetry have been used to monitor and assess the oxygenation status of patients before and during a discontinuation trial. In general, a PaO₂ of more than 60 mm Hg (or of more than 55 mm Hg for patients with COPD with carbon dioxide retention) with an FiO₂ of less than 0.40 to 0.50 and a PEEP of 5 to 8 cm H₂O or less should be adequate for ventilator discontinuation.^3,7 The PaO₂/FiO₂ ratio should be 150 to 200 mm Hg or more.³ With these values, a normal hemoglobin level, a normal oxygen saturation (SaO₂), and adequate cardiac output and tissue perfusion are assumed. Specific indices used to assess oxygenation status are found in Table 47-1.

Acid-Base Balance

Ideally the patient should have a normal acid–base balance (i.e., a pH of 7.35 to 7.45), and abnormalities in acid–base status should be corrected, if possible, before weaning. Patients with metabolic acidosis often have an increased ventilatory drive that can make weaning difficult. Patients who have metabolic alkalosis or those who have been mechanically hyperventilated for several days may have a reduced ventilatory drive. In these cases, a gradual method of discontinuing ventilatory support should be considered.

Metabolic Factors

Metabolic factors primarily affect discontinuation in those patients who require long-term ventilatory support. Although nutritional factors are important for all patients, they are unlikely to affect discontinuation in those who only require short-term ventilatory support. Nutrition should be adequate to maintain respiratory muscle mass and contractile force.¹⁶ Feeding should be adjusted according to individual patient needs; most patients need 1.5 to 2.0 times their resting energy expenditure.³³ In addition, protein intake should be between 1 and 1.5 g/kg per day. Excessive carbohydrate feeding can increase carbon dioxide production and may precipitate acute hypercapnic respiratory failure.¹⁶ Parenteral nutrition solutions that contain amino acid formulations (e.g., arginine/lysine) can cause metabolic acidosis and thus increase ventilatory demand.³³ Metabolic rate can increase as a result of fever or sepsis. Increased WOB, shivering, seizures, and agitation can also increase oxygen demand and should be evaluated.

Renal Function and Electrolytes

Adequate renal function is required to maintain acid–base homeostasis, electrolyte concentrations, and fluid balance.³⁴ The patient ideally should have an adequate urine output (i.e., more than 1000 ml/day), and there should be no inappropriate weight gain or edema.

Renal insufficiency can lead to metabolic acidosis, which increases respiratory drive. Electrolyte disorders can impair ventilatory muscle function.3,16 Key electrolytes should be normal (i.e., magnesium, 1.8 to 3 mEq/L; phosphate, 2.5 to 4.8 mEq/L; potassium, 3.5 to 5 mEq/L); see Chapter 16 for details. Fluid overload can lead to congestive heart failure and pulmonary edema, which may impair pulmonary gas exchange.

Cardiovascular Function

Adequate cardiovascular function is needed to provide sufficient oxygen delivery to the tissues. Cardiac rate and rhythm and blood pressure should be evaluated.3,16 Tachycardia (i.e., a heart rate of more than 100 to 120 beats/min) and bradycardia (i.e., a heart rate of less than 60 to 70 beats/min) should be controlled. The presence of arrhythmias, hypotension (i.e., a blood pressure of less than 90/60 mm Hg), and severe hypertension (i.e., a blood pressure of more than 180/110 mm Hg) should be evaluated carefully before the discontinuation of ventilatory support is considered.^3,19

Cardiac output and index measurements as well as central line and pulmonary arterial pressures (i.e., central venous pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure) may be helpful for the evaluation of cardiovascular function. Left ventricular dysfunction, myocardial ischemia, and cardiovascular instability are associated with decreased discontinuation success.3,21 Table 47-2 provides criteria for confirming cardiovascular stability. However, very few patients without primary cardiovascular dysfunction have pulmonary artery catheters in place. The assessment of cardiac output is usually by noninvasive means, and only arterial and central venous pressures are generally available.

TABLE 47-2

Criteria for Confirming Cardiovascular Stability

Criterion	Normal Value	Values That May Be Inconsistent With Weaning
Heart rate (beats/min)	60 to 100	<60, >120
Blood pressure (mm Hg)	90/60 to 150/90	<90/60, >180/110
(L/min)	4 to 8
Cardiac index (L/min−1·m2)	2.5 to 4	<2.1
Cardiac rhythm	No major arrhythmias present	Tachycardia, bradycardia, multiple premature ventricular contractions, heart block
Hemoglobin (g/dl)	12 to 15	Anemia, <10
Hematocrit	40% to 50%
No angina present
No lactic acidosis

Psychologic Factors and Central Nervous System Assessment

Adequate CNS function is needed to ensure stable ventilatory drive, adequate secretion clearance (i.e., coughing and deep breathing), and the protection of the airway (i.e., gag reflex and swallow). In addition, the level of consciousness, dyspnea, anxiety, depression, and motivation can affect discontinuation success.3,5

The patient ideally is awake and alert, free of seizures, and able to follow instructions.3,34 Patients should have an intact central drive to breathe and peripheral nerve function. Brainstem strokes, electrolyte disturbances, sedation, neuromuscular blocking agents, and narcotic drugs can impair the central neurologic control of ventilation.³ Mental status is a good predictor of discontinuation success, and patients who are not alert are at risk for upper airway obstruction, aspiration, and secretion retention. Obtunded patients should, at a minimum, have an adequate gag reflex and cough. Decreased levels of consciousness are associated with aspiration after extubation. The level of consciousness is affected by the use of narcotic, sedative, and analgesic drugs. Drugs with CNS depressant effects should be discontinued, if possible, before the withdrawal of ventilatory support and extubation.¹⁶ Protocols to reduce sedation and the daily cessation of sedative drugs may reduce weaning time^12,35,36 (see the section on Spontaneous Awaking Trials). The use of neuromuscular blocking agents to allow for controlled ventilation should be avoided, because they may prolong mechanical ventilation.³⁷

Psychologic factors may be among the most important nonrespiratory contributing factors that lead to ventilator dependence.³ Fear, anxiety, and stress should be minimized, and frequent communication among the staff, the patient, and the patient’s family can be helpful.³ Box 47-5 summarizes nonrespiratory factors that affect discontinuation success.

Integrated Indices

Many factors are associated with discontinuation success. In an analysis of 217 patients, discontinuation success could be accurately predicted in about 75% of the patients when multiple predictors were combined.²⁴ For all patients, regardless of diagnosis, days of mechanical ventilation (DMV), f/V_t; MIP, P_0.1, maximum expiratory pressure, and VC—when used in combination—were the best predictors.²⁴ For patients with acute respiratory failure, the best predictors were DMV, P_0.1/MIP, MIP, f/V_t, and age (76.1% accurate); for patients with COPD, the best predictors were DMV, f/V_t, P_0.1, P_0.1/MIP, MIP, and age (93.9% accurate); and for patients with neuromuscular disease, MIP, maximum expiratory pressure, f/V_t, and P_0.1 were the best predictors (73.9% accurate).²⁴ Integrated indices improve prediction by combining several measures of ability to breathe without ventilatory support. Current examples of integrated indexes include the CROP score, the Adverse Factor/Ventilator Score, the weaning index, and the Burns Weaning Assessment Program.^7,19 The CROP score combines measures of ventilatory load, respiratory muscle strength, and gas exchange.^7,23

The Adverse Factor/Ventilator Score combines ratings of 15 adverse factors, including hemodynamic values, infection, nutrition, and neurologic/psychiatric state, with ratings of six ventilator factors, including FiO₂, compliance, minute ventilation, and rate.¹⁹ The weaning index combines measures of ventilatory strength, endurance, and efficiency of gas exchange.¹⁹ A weaning index of less than 4 suggests successful discontinuation from mechanical ventilation.^18,32 The Burns Weaning Assessment Program is a 26-item assessment that combines 12 general and 14 respiratory factors into a single score.¹⁹ Although integrated indices appear promising, no single index has emerged as superior for use in diverse patient populations. Despite the success of these integrated indices in very specific settings, the best approach to determining if a patient can be successfully discontinued from ventilatory support is the patient’s performance on spontaneous breathing trials. All patients should be assessed daily, and their ability to breathe spontaneously should be the primarily variable to determine if the ventilator can be discontinued.

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