GCS = Glasgow coma scale; Hgb = hemoglobin; HR = heart rate.

Adapted from MacIntyre NR, Cook DJ, Ely EW Jr, et al. Evidence-based guidelines for weaning and discontinuing ventilatory support: a collective task force facilitated by the American College of Chest Physcians; the American Association for Respiratory Care; and the American College of Critical Care Medicine. Chest. 2001;129:375S-95S.

There are occasions when the decision to remove an endotracheal tube is considered overly aggressive, while at other times the decision making may be considered too conservative and slow. If the tube is taken out prematurely in an overly aggressive fashion, the major problem is the potential for a difficult reintubation if it is necessary for management of extubation failure. Often, the reintubation may be emergent or urgent. A difficult reintubation predisposes the patient to aspiration, may result in hypoxemia and hypoxic brain injury, and increases the risk for pneumonia. The likelihood of developing pneumonia is 3 to 6 times more likely with a difficult intubation. On the other hand, if the extubation process is delayed related to a slow, overly conservative weaning strategy, it is likely that the patient was kept on the ventilator for a more prolonged period of time. Prolonged mechanical ventilation (MV) can increase the risk of developing pneumonia; put the airway at risk for developing tracheal stenosis, tracheomalacia, and other airway-related injuries; and increase the risk of arrhythmias.

Weaning Failure

The acceptable extubation failure rate depends on the definition used. At this time there is no uniformly accepted definition of extubation failure. Some experts define extubation failure as the need for reintubation within 24 hours, whereas others define it as reintubation within 48 hours of extubation. The concept is further complicated by the use of noninvasive positive pressure ventilatory support as a means to address respiratory failure. Some consider the need for any type of respiratory support (intubation, positive pressure ventilatory support) as evidence of liberation failure. Further complicating the definition is the need for reintubation for a new bout of respiratory failure or other complicating condition which is unrelated to the original condition for which the patient was previously on mechanical ventilatory support. Most studies report a 5% to 15% reintubation rate, which has become the accepted range for liberation failure. Clinicians who need to reintubate <5% of weaned patients are probably too conservative in their approach to weaning patients from ventilatory support. On the other hand, clinicians who have to reintubate >20% of their extubated patients are probably too aggressive.

Common reasons for weaning failure include uncorrected physiology, decreased respiratory drive (which may be iatrogenic), and unanticipated gas exchange abnormalities.² Problems with the respiratory pumps can be secondary to increased respiratory load as a consequence of increased carbon dioxide (CO₂) production, which may result from overfeeding, fever, and hyperthyroidism. In contrast to increased CO₂ production, there may be problems with the respiratory muscles (as can result from neuromuscular disease), electrolyte abnormalities, and myxedema coma. All of these conditions may contribute to weakness and ineffective CO₂ elimination. Patients may also lack the necessary cardiac or pulmonary function for successful liberation from mechanical ventilatory support.

Some patients fail the weaning process secondary to occult ischemic cardiac disease, which only becomes apparent when they are subjected to the increased work of breathing associated with the liberation process. There are intrathoracic pressure changes that occur dependent on whether the patient is breathing spontaneously or receiving continuous positive-pressure ventilation. Spontaneous ventilation increases cardiac preload related to increased venous return as a consequence of reduced intrathoracic pressure. The changing intrathoracic pressure and physiology there may result in various changes in cardiac function. When a patient is being weaned from positive-pressure ventilation, there is increased myocardial oxygen (O₂) demand and a 12% increase in the rate pressure product. Total body O₂ consumption can increase 15% to 25% as a consequence of the liberation process. The intrathoracic pressure changes going from positive pressure to more negative pressure results in an increase in venous return, which may be beneficial if the patient’s blood pressure has been low. On the other hand, it could put a patient who has tenuous cardiac function and borderline heart failure into more florid heart failure because the increased preload moves the patient further to the right side of their Frank-Starling curve. The weaning process also increases left ventricular afterload. In addition, some patients may have occult cardiac ischemia that does not come to light until they begin the process of weaning from the ventilator. An electrocardiogram performed on a patient who is not tolerating the separation process may demonstrate evidence of previously undiagnosed ischemia. In this situation, a percutaneous coronary intervention may be needed to correct the vascular abnormality and, once corrected, will facilitate the weaning process. In addition, the act of weaning may increase the level of circulating catecholamines, especially in patients who are fearful, anxious, or in pain, which may place additional demands on the heart or produce arrhythmias.

Patients who lack adequate function of their respiratory muscles may need prolonged ventilatory support until this situation has been improved. As they gain more respiratory muscle function and their body corrects the underlying abnormalities, they can then assume more of the respiratory load and likely be freed from the ventilator.³ Another factor that may interfere with the liberation process may relate to a psychological fear of or anxiety about extubation, perhaps due to a previous negative experience.

Clinicians should also be prepared for unplanned extubations. A prospective study looked at the need for reintubation after patients deliberately or accidentally pulled out their ETTs^.4 The need for reintubation was higher in patients who accidentally pulled out their endotracheal tubes than in those who deliberately took them out (77% vs 37%). When these investigators looked at unplanned extubations in patients during the weaning process, only 16% required reintubation. This speaks to the notion that patients sometimes know more about when the time is right for extubation. On the other hand, reintubation was necessary for 82% of patients who were not in the weaning process when their ETTs were removed.

Evidenced-Based Weaning Recommendations

In 2001, the Evidence-Based Guidelines for Weaning and Discontinuing Ventilatory Support were developed by a collective task force representing the American College of Chest Physicians, the American Association of Respiratory Care, and the American College of Critical Care Medicine. The task force reviewed the published literature and data analysis provided by the Agency for Healthcare Policy and Research and McMaster University Evidence-Based Practice Center to develop the guidelines.⁵ Dr. MacIntyre and co-workers used a grading system for their recommendations with grades ranging from A to C. Grade A recommendations were based on scientific evidence from well-designed, well-conducted, controlled clinical trials (randomized and non-randomized) with statistically significant results that consistently supported the guideline recommendations. Grade B recommendations were based on scientific evidence provided by observational studies or by controlled trials with less consistent results to support the guideline recommendations. Grade C recommendations were on expert opinion in support of the guideline recommendation, but scientific evidence either provided inconsistent results or was lacking.⁵

Evidence-based guidelines typically use a meta-analysis of various prospective, randomized controlled trials to add strength to their recommendation. The meta-analysis is designed to correct for random errors that may have occurred during the conduct of the component studies. Unfortunately, some clinical studies may contain systematic errors which complicate the design, conduct, or results of the trial, and these errors are subsequently amplified when the studies are combined in a meta-analysis. As a result, the meta-analysis lacks validity.⁶ Dr. Tobin and Dr. Jubran have recently critiqued the 2001 evidence-based weaning guidelines and raised significant concerns over the potential for systematic errors in the various studies included in the meta-analysis. The basis for the potential systematic errors includes the fact that subject-selection bias exists because patients who are likely to be weaned are often specifically targeted for inclusion in weaning trials. Second, weaning trials are typically not conducted by blinded investigators. They cannot help but know which patients are weaning and which ones are doing well. Third, many of the trials do not use the same definition for success and/or failure. Sometimes the weaning protocol used in a study predetermines which group will be extubated fastest simply as a function of the algorithm that is being followed as part of the study protocol. The specific recommendations that come from the task force and the grade each recommendation received follow:

• Recommendation 1 calls on clinicians to search for and address all of the causes that may be responsible for prolonged MV in patients who require more than 24 hours of ventilatory support or in whom weaning attempts fail. Furthermore, finding and reversing these causes are an integral part of the weaning process. The evidence for this recommendation was given a grade B.
  
• Recommendation 2 suggests that patients receiving MV should undergo formal assessment of discontinuation potential if the following are met: evidence that the reason for MV or the cause of a patient’s respiratory failure has partially or completely reversed, evidence of adequate oxygenation, hemodynamic stability, and the patient’s ability to initiate an inspiratory effort.⁵ The common clinical conditions to address and ensure are met to indicate readiness to begin the liberation process are listed in Table 1. This recommendation’s grade was a B.
  
• Recommendation 3 calls for a formal discontinuation assessment of likelihood to wean to be performed during a spontaneous breathing trial (SBT), rather than while the patient is receiving substantial ventilatory support.⁵ This initial assessment should be in the form of a brief SBT to assess the patient’s ability to complete a formal SBT. This should be performed at the patient’s bedside. The clinician should assess the patient’s tolerance by observing the respiratory pattern, gas exchange, hemodynamic stability, and comfort during the trial. Once the clinician decides that the patient is tolerating this process, it is time to embark on a 30- to 120-minute SBT. If the patient passes the 30 – 120 minute SBT, the clinician should make a prompt assessment for the removal of the endotracheal tube and discontinuation of the ventilatory support. This recommendation was given a grade A.

In the past, clinicians have used multiple measurements to help determine a patient’s “weanability.” Some of these parameters include measuring the minute ventilation, negative inspiratory force, maximal inspiratory pressure, mouth occlusion pressure of 0.1 second after the onset of inspiratory effort, and the CROP index (a composite score including compliance, respiratory rate, oxygenation, and pressure). A simple ratio of the respiratory rate or frequency divided by the tidal volume in liters (f/V_t) has proved to be a useful tool to predict a patient’s readiness for extubation.^6a This ratio has often been termed the rapid shallow breathing index (RSBI). Although this seems very basic, it has been known for many decades that in patients who develop respiratory distress or failure, the respiratory rate increases and the tidal volume decreases. This pattern of rapid shallow breathing can result in hypercapnic respiratory acidosis and typically results in a need for intubation.

When investigators evaluated f/V_t against other tests for predicting successful weaning of patients from ventilation, it had better sensitivity, specificity, and positive and negative predictive value.⁷ Monitoring the f/V_t to help judge tolerance of a SBT helps ensure successful completion and minimize the possibility of having to intubate patients on an emergency basis. Other objective criteria for a successful SBT are gas exchange acceptability, hemodynamic stability, and a stable ventilatory pattern.

Several studies have compared weaning methods to determine which one leads to faster discontinuation of the ventilator. One prospective, randomized trial compared intermittent MV (IMV) with successive reductions, pressure-support ventilation with progressive reduction, intermittent SBTs, and once-daily SBT.⁸ The median duration of weaning was 5 days for IMV, 4 days for pressure-support ventilation, and 3 days for both intermittent SBTs and once-daily SBT. Consequently, either multiple SBTs or a single SBT can be used to remove the ETT quicker. However, since there is a potential for multiple SBTs to deplete the energy stores and decrease function of the respiratory muscles, most recommend a single SBT per day. Using the technique of SBTs to guide the weaning process, reported studies demonstrate a success rate of over 77%. Some reports document success rates of 95%.

Studies have evaluated whether there is additional benefit associated with using a longer spontaneous breathing trial to determine extubation readiness. A prospective study of a 30 minute compared to 120 minute spontaneous breathing trial reported a similar success rate.⁹ Based on this observation, the duration of the SBTs used to assess a patient’s ability to be liberated from ventilatory support will depend on the individual patient’s clinical condition and the clinician’s comfort with the process.

• Recommendation 4 governs that the removal of the artificial airway from the patient who has successfully passed an SBT or weaning assessment trial should be based on an assessment of airway patency and the ability of the patient to protect their airway.⁵ Because there is not a lot of data to support this recommendation, it earns a grade of C, which means that it is based predominantly on consensus opinion. This recommendation makes clinical sense, which is probably why a formal study to investigate this hypothesis has not as yet been completed.

Laryngoedema, laryngospasm, and even upper airway edema are some of the problems that may necessitate a more prolonged intubation after successfully passing a SBT. In the setting of laryngoedema or upper airway edema, clinicians have used the “cuff-leak test” to determine if a patient is at an increased risk of developing post-extubation airway obstruction. During the test, the balloon cuff of the endotracheal tube is deflated while the patients is ventilated with a known tidal volume. If there is a leak >110 mL, some believe that the airway is sufficiently patent and there is not a significant amount of airway narrowing or edema. Unfortunately, this test has not been demonstrated to reliably predict airway narrowing or the absence of airway issues post-extubation.

For those patients in whom post-extubation complications are of concern, there is at least one report that pre-dosing with dexamethasone for 24 to 48 hours will decrease the likelihood of significant laryngoedema and need for re-intubation. These complications are rare, so one must weigh the potential risks against the potential benefits of this management strategy.

Another concern is whether a patient is able to protect their airway. Many times this is related to their level of consciousness, but it is more a function of an adequate cough reflex. Clinicians may assess the cough reflex by inserting a suction catheter through the ETT and evaluate the patient’s cough. In addition to an adequate cough, the clinician must also assess whether the patient has an excessive amount of tracheobronchial secretions which might lead to respiratory compromise once the ETT is removed. Although it is not very scientific, the generally accepted rule states that if a patient does not need to be suctioned for at least 2 hours, then that patient most likely does not have excessive secretions. Remember, however, that just having the ETT in the airway oftentimes stimulates secretions, as does the use of a humidification system and/or a nebulizer.

• Recommendation 5 states that for patients who fail an SBT, the reason for failure should be determined and corrected.⁵ Once the reason is corrected, a repeat SBT should be performed every 24 hours (unless the reason is related to recovery from sedation or prolonged anesthetic effect, in which case the trial can be repeated later the same day). There is no point in restressing the patient later that day with a repeat SBT because it does not lead to earlier removal of the ETT. In fact, performing an SBT within 24 hours may actually make the patient more tired by depleting the respiratory muscles. The more depleted and deconditioned a patient is, the more time it may take to recover to pass the next trial. This recommendation was given a grade of A.
  
• Recommendation 6 states that patients who fail an SBT should receive a stable, nonfatiguing, comfortable form of ventilatory support until it is time for the next SBT.⁵ Table 2 delineates modes of partial ventilatory support. Clinicians should choose a mode that the patient tolerates well and with minimal sedation requirements. This recommendation was given a grade of B, based on the quality of supporting evidence.

Table 2. Modes of Partial Ventilatory Support

Adapted from MacIntyre NR, Cook DJ, Ely EW Jr, et al. Evidence-based guidelines for weaning and discontinuing ventilatory support: a collective task force facilitated by the American College of Chest Physicians; the American Association of Respiratory Care; and the American College of Critical Care Medicine. Chest. 2001;129:375S-95S.

• Recommendation 7 calls for the use of anesthesia and sedation strategies coupled with ventilator management that will facilitate early extubation in post-operative patients.⁵ This is relevant for patients returning from surgical procedures who should be provided with a sedation/analgesia strategy and a ventilatory support mode that allows them to be rapidly weaned as soon as possible after the surgical procedure and recovery from the anesthetic. This recommendation was given a grade of A.
  
• Recommendation 8 suggests that weaning or discontinuation protocols designed for nonphysician health-care professionals should be developed and implemented.⁵ Several reports have demonstrated that empowering nonphysician heath-care professionals to evaluate ventilated patients for readiness to wean and then using a liberation protocol or strategy results in a shorter time to extubation and reduced ventilatory support duration.^10,10a In addition, using a strategy to optimize sedation and avoid oversedation also benfits the liberation process. This recommendation has good supporting evidence that warrants a grade of A.

Included in the supporting data for this recommendation is a randomized controlled trial which demonstrated that having a weaning protocol under the direction of a nonphysician weaning team led to faster extubation for ventilated patients.¹⁰ Despite having more severe disease, patients assigned to the intervention group received MV for a median of 4.5 days compared with 6 days for patients in the control group. Weaning time was 1 day in the intervention group versus 3 days for the control group.

Sedation Protocols

The Society of Critical Care Medicine¹¹ published its guidelines for the sustained use of sedatives and analgesics in critically ill adults in 2002. Many studies have shown that using a sedation protocol decreases duration of MV¹² as well as length of ICU and hospital stay.¹³ Kress and colleagues¹⁴ reported that using a sedation protocol that included a daily awakening and evaluation of a patient’s sedation requirements resulted in multiple benefits.¹⁴ In this prospective controlled trial, 128 patients receiving MV were randomized to either daily interruption of sedation until the patient was awake versus sedation management at the clinician’s discretion. The duration of MV was 4.9 days for the group subjected to daily awakening versus 7.3 days in the control group. The median length of ICU stay was 6.4 days for the awakened group compared with 9.9 days for the control group. Another benefit of the reduced sedation, or “sedation vacation,” was less need for studies to evaluate the unresponsive patient or patient with altered neurologic status. Thus, there were fewer head CT scans and other investigations to evaluate patients for altered mental status.

Additional studies combined the use of a sedation protocol involving a daily interruption with the use of weaning protocols. Girard and colleagues¹⁵ evaluated the use of a sedation protocol paired with an SBT versus usual care plus an SBT on weaning outcomes. The intervention group used less benzodiazepine, but this group also had more unplanned extubations. Despite the increase in unplanned extubations, the sedation protocol group had a significantly improved rate of extubation and discharge from the ICU compared to the control group. Patients in the sedation protocol intervention group were also discharged earlier from the ICU (9.1 vs 12.9 days) and the hospital (14.9 vs 19.2 days) than their counterparts in the control group. The sedation group also had a significantly better survival rate over the one-year follow-up compared to the control group.

Issues in Prolonged Mechanical Ventilation

• Recommendation 9 recommends that a tracheotomy be considered when it becomes apparent that the patient will require prolonged ventilatory assistance after an initial period of stabilization. The patient should also be evaluated to determine if he/she will likely benefit from one of the following additional benefits associated with having a tracheotomy: 1) Need for less sedation than with a translaryngeal tube; 2) The potential for improved respiratory mechanics as may result from decreased dead space; and 3) The potential for psychological benefit from the ability to now eat, speak, communicate, improve mobility, or participate in physical therapy.⁵ This recommendation was graded B.

Previously, the best time to perform a tracheotomy in a patient receiving MV was controversial. The general consensus was that it was best to wait 21 days to do a tracheotomy. Today, with the availability and ease of performing a percutaneous tracheotomy and the psychological benefit to patients having one, tracheotomies are being performed earlier in the care process. One of the benefits of having a tracheotomy in place for prolonged ventilatory support is that weaning is much easier because the biggest fear, not having an airway, is now gone. Weaning involves disconnecting the tracheotomy, an easily reversed process. Most clinicians are very comfortable with this approach. Several studies have looked at the impact of tracheotomy on MV outcome, and some of these are included in Table 3.

Table 3. Impact of Tracheotomy on Mechanical Ventilation Outcome

LOS = length of stay.

Adapted from MacIntyre NR, Cook DJ, Ely EW Jr, et al. Evidence-based guidelines for weaning and discontinuing ventilatory 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. 2001;129375S-95S.

• Recommendation 10 suggests that unless there is evidence for a clearly irreversible process, a patient who is receiving mechanical ventilatory support for a prolonged time should not be considered ventilator dependent until there have been 3 months of failed weaning attempts.⁵ This recommendation was given a grade of B.
  
• Recommendation 11 calls on critical-care practitioners to become familiar with facilities in their community or even their hospital that provide prolonged ventilatory support to patients who have failed weaning attempts.⁵ Thus, when medically stable for transport, patients in whom multiple weaning attempts have failed should be transferred to these facilities. This recommendation received a grade of C. At this time, the standard of care for patients who fail multiple attempts to wean from mechanical ventilatory support but are otherwise clinically stable require that the patient be transferred to a prolonged ventilatory support facility where slower-paced weaning strategies can be used.
  
• Recommendation 12 recommends that weaning strategies employed in patients with prolonged MV should be slow paced and include gradually lengthening of SBT^.5 Post-ICU prolonged weaning strategies are listed in Table 4. This recommendation is based primarily on consensus opinion and earned a grade of C.

Table 4. Post-ICU Ventilation Weaning Strategies

AC = Assist-control; PSV = pressure support ventilation; TTO = transtracheal oxygen; TP = T-piece; VTM = Venti-Trach mask (tracheal collar).

Adapted from MacIntyre NR, Cook DJ, Ely EW Jr, et al. Evidence-based guidelines for weaning and discontinuing ventilatory 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. 2001;129:375S–95S.

Critically ill patients who have received prolonged mechanical ventilatory support are at risk for muscle weakness. They may become deconditioned from the prolonged time of inactivity or may have metabolic reasons for muscle dysfunction related to hypophosphatemia, hypocalcemia, or hypomagnesemia. In addition, critically ill patients are at risk to develop critical illness polymyopathy-polyneuropathy, which can adversely affect respiratory muscle function and the weaning process.^15a In addition, it has recently been demonstrated that in the setting of controlled MV where there is an absence of respiratory muscle activity for 18 hours or more, there may be atrophy of both the slow and fast twitch muscle fibers of the diaphragm and respiratory muscles.^15b The decrease in muscle fibers was a consequence of increased proteolytic activity and would be expected to have a significant impact on respiratory muscle function.

A topic not addressed by the guidelines is whether noninvasive positive-pressure ventilation (NIPPV) can be used to support the patient who develops respiratory distress after the ETT has been removed.^16,17,18,19 Some feel that NIPPV is a suitable rescue strategy for patients who develop post-extubation respiratory distress/ failure. Others, however, would argue for early re-intubation. Esteban and colleagues¹⁶ conducted a prospective, randomized trial involving 221 patients with respiratory distress post-extubation and compared NIPPV with standard medical treatment, including early re-intubation, if indicated. They found that patients with post-extubation respiratory failure who were treated with NIPPV had a significantly higher mortality rate compared to those who received standard medical treatment, which included early re-intubation when indicated (25% vs 14%).¹⁶ The authors concluded that using NIPPV in the rescue mode either delayed effective therapy or caused other problems, such as myocardial events, which might have been responsible for the observed increased mortality. A subsequent trial by Ferrer and coworkers¹⁷ prospectively randomized 162 patients who were judged to be at high risk for re-intubation after successful weaning. The high-risk patients were defined by age greater than 65 years, cardiac failure as the cause of intubation, or an APACHE II score > 12 on the day of extubation. In this study the NIPPV who were high risk and had evidence of hypercapnia had a significantly improved survival over 90 days compared to the standard medical management patients.¹⁷ A multicenter, randomized trial of NIPPV versus standard medical management in high risk patients post extubation also reported significant benefit associated with early use of NIPPV.¹⁸ The high-risk population in this trial were defined by failure to pass at least 1 prior weaning trial, the presence of congestive heart failure or other co-morbidity, weak cough, stridor at the time of extubation, or a PaCO₂ ≥ 45 mm Hg after extubation. The use of early NIPPV decreased the need for reintubation (8% vs 24%, p=0.027). This was an important benefit since the need for reintubation was associated with a significantly increased risk for mortality (63% vs 3%, p<0.001).¹⁸ A recent meta-analysis on the use of NIPPV for post-extubation respiratory failure has concluded that there is still uncertainty regarding the benefit, but there was benefit in using NIPPV to prevent post-extubation respiratory failure.¹⁹ It does appear that there is a defined population of high-risk patients who might benefit from the use of NIPPV in the management of post-extubation respiratory failure, but this technique will not be beneficial, and may be harmful, in other groups of patients.

Summary

Clinicians must assess patients on a daily basis for readiness to wean and use a protocol-directed weaning strategy. If an SBT fails, clinicians should allow the patient to rest overnight and must correct any abnormality before a repeat SBT is attempted. They should incorporate a protocol for sedation and analgesia in their weaning strategies. Finally, clinicians should be very cautious about using NIPPV in weaning failure. If they decide beforehand that NIPPV is the best way to remove the ETT, there is support for that. However, if they are using it as a rescue mode, be aware that it can increase mortality in some patients and may be beneficial in others.

References

1. Esteban A, Alia I, Ibanez J, et al. Modes of mechanical ventilation and weaning. A national survey of Spanish hospitals. The Spanish Lung Failure Collaborative Group. Chest. 1994;106:1188–1193.

2. Chao DC, Scheinborn DJ. Weaning from mechanical ventilation. Crit Care Med. 1998;14: 799–817.

3. MacIntyre NR. Evidence-based ventilator weaning and discontinuation. Respir Care. 2004;49:830–836.

4. Betbese AJ, Perez M, Bak E, et al. A prospective study of unplanned endotracheal extubation in intensive care patients. Crit Care Med. 1998;26:1180–1186.

5. MacIntyre NR, Cook DJ, Ely EW Jr, et al. Evidence-based guidelines for weaning and discontinuing ventilatory 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. 2001;129:375S–95S.

6. Tobin MJ, Jubran A. Meta-analysis under the spotlight: focused on a meta-analysis of ventilator weaning. Crit Care Med. 2008:36:1–7.

6a. Yang KL, Tobin MJ. A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N Engl J Med. 1991;324:1445-1450.

7. Vallverdu I, Calaf N, Subirana M, et al. Clinical characteristics, respiratory functional parameters, and outcome of a two-hour T-piece trial in patients weaning from mechanical ventilation. Am J Respir Crit Care Med. 1998;158:1855–1862.

8. Esteban A, Frutos F, Tobin MJ, et al. A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group. N Engl J Med 1995;3332:345–350.

9. Esteban A, Alia I, Tobin MJ, et al. Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med. 1999;159:512–518.

10. Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med. 1996;335:1864–1869.

10a. Kollef MH, Shapiro SD, Silver P, et al. A randomized, controlled trial of protocol-directed versus physician-directed weaning from mechanical ventilation. Crit Care Med. 1997;25:567-574.

11. Jacobi J, Fraser GL, Coursin DG, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adults. Crit Care Med. 2002;30:119–141.

12. De Jonghe B, Bastuji-Garin S, Fangio P, et al. Sedation algorithm in critically ill patients without acute brain injury. Crit Care Med. 2005;33:120–127.

13. Brook, AD, Ahrens TS, Schaiff R, et al. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med. 1999;27:2609–2615.

14. Kress JP, Pohlman AS, O’Connor MF, et al. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342:1471–1477.

15. Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (awakening and breathing controlled trial): a randomised controlled trial. Lancet. 2008;371:126–134.

15a. Schweickert WD, Hall J. ICU-acquired weakness. Chest. 2007;131:1541-1549.

15b. Levine S, Nguyen T, Taylor N, et al. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med. 2008;358:1327-1335.

16. Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med. 2004;350:2452–2460.

17. Ferrer M, Valencia M, Nicolas JM, et al. Early noninvasive ventilation averts extubation failure in patients at risk: a randomized trial. Am J Respir Crit Care Med. 2006;173:164-170.

18. Nava S, Gregoretti C, Fanpulla F, et al. Noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients. Crit Care Med. 2005;33:2465-2470.

19. Agarwal R, Aggarwal An, Gupta D, et al. Role of noninvasive positive-pressure ventilation in postextubation respiratory failure: a meta-analysis. Respir Care. 2007;52:1472-1479.

Self-Assessment

1. Which one of the following clinical conditions is not a common reason for weaning failure?
   

   (a) Uncorrected physiology

   
   

   (b) Pneumonia

   
   

   (c) Decreased respiratory drive

   
   

   (d) Unanticipated gas-exchange abnormalities

   
   
   
2. How soon after a failed spontaneous breathing trial should a repeat  spontaneous breathing trial be performed?
   

   (a) Every 2 hours

   
   

   (b) Every 12 hours

   
   

   (c) Every 24 hours

   
   

   (d) Every 30 hours

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