◆ Several studies suggest that most patients weaned successfully could have tolerated the weaning attempts had they been initiated a day or more earlier. Such data emphasize the need for the early use of screening tests.
◆ A screening test should have a high sensitivity. The ratio of respiratory frequency to tidal volume (f/VT) has been evaluated in more than 25 studies—its average sensitivity is 0.89.
◆ Weaning involves undertaking three diagnostic tests in sequence, measurement of predictors, a weaning trial, and a trial of extubation.
◆ Of the techniques used for a weaning trial, IMV has been repeatedly shown to be inferior to the use of T-tube trials or pressure support.
◆ Six randomized trials have evaluated the usefulness of protocols in the management of weaning. Three revealed no benefit, two had major methodological problems, leaving only one supporting the use of protocols.
Although mechanical ventilation is often lifesaving, the high risk of complications makes it imperative to disconnect patients from the ventilator at the earliest possible time . This process is usually referred to as weaning, an unfortunate term because the word means a gradual reduction in a process . Most patients move quite abruptly from a period of high-level support to unassisted breathing.
The timing of this process is critical. Several randomized controlled trials (RCTs) have revealed most patients who received mechanical ventilation for a week or longer were able to tolerate ventilator discontinuation on the first day that weaning-predictor tests were measured [3,4]. Many of these patients may have tolerated extubation a day or so earlier.
Many physicians view weaning predictors as something to perform at the point they think a patient might be able to tolerate disconnection from the ventilator. However, weaning predictors have the greatest potential for enhancing clinical management if performed at a time when physicians have considerable doubt as to whether or not a patient is ready for ventilator disconnection.
One of the main sources of weaning delay is the failure to think the patient just might come off the ventilator. Psychological research suggests much of this delay in ventilator weaning results from clinicians being overconfident in their intuition that a patient is not ready for a weaning trial . Another source of error is the failure to pay close attention to pretest probability, i.e. failure to recognize the importance of Bayesian principles in clinical-decision making.
Assessment of patient readiness for weaning
By alerting physicians to a patient’s readiness to tolerate unassisted ventilation—hours or days before he or she would otherwise order a spontaneous breathing trial—weaning-predictor tests circumvent the cognitive errors inherent in clinical decision-making .
Weaning-predictor tests function solely as a screening test. The goal of a screening test is not to miss anybody with the condition under consideration. It should have a low false-negative rate and a higher false-positive rate is acceptable . An ideal screening test has a high sensitivity [2,5].
Weaning uses three diagnostic tests in sequence—measurement of predictors, a weaning trial, and a trial of extubation . The sequential nature of the testing leads to particular problems in studies undertaken to investigate the reliability of a predictor test. One is spectrum bias where a new study population contains fewer (or more) sick patients than the population in which a diagnostic test was originally developed [5,6]. A second is test-referral bias, where the results of a test under evaluation are used to select patients for a reference-standard test, e.g. passing a weaning trial that leads to extubation [5,6]. A third factor is base-rate fallacy [6,7]. Consider a diagnostic test for a disease that has a false-positive rate of 5% and false-negative rate of 0%, and the incidence of the disorder (under consideration) is 1 per 1000 persons. A randomly selected person undergoes diagnostic testing. The result comes back positive. What is the chance this person has the disease? Most physicians answer 95%. The correct answer is 1.96% . Physicians who answer 95% are failing to take into account the pretest probability of the disorder. Thus, they fall into the trap of base-rate fallacy.
Pretest probability is the estimate of the likelihood of a particular condition (weaning outcome) before a diagnostic test is undertaken . Post-test probability (typically expressed as positive- or negative-predictive value) is the new likelihood after the test results are obtained. A good diagnostic test achieves a marked increase (or decrease) in the post-test probability (over pretest probability) (Fig. 102.1). For every test the change between pre- and post-test probability is determined by Bayes’ theorem . Three factors determine the magnitude of the pre- to post-test change—sensitivity, specificity, and pre-test probability. Sensitivity and specificity are commonly assumed to remain constant for a test. In truth, test-referral bias, a common occurrence in studies of weaning tests, leads to major changes in sensitivity and specificity . Likewise, major changes in pre-test probability arise as a consequence of spectrum bias .
Frequency-to-tidal volume ratio
Weaning-failure involves several different physiological abnormalities . The combination of a low tidal volume and elevated respiratory frequency is recognized as the physiological hallmark of weaning failure (Fig. 102.2) . Patients who fail a weaning trial typically demonstrate rapid shallow breathing in the first few minutes after they are disconnected from the ventilator  quantified as the ratio of respiratory frequency to tidal volume (f/Vt) . The higher the f/VT, the more severe the rapid, shallow breathing and the greater the likelihood of unsuccessful weaning. An f/VT of 100 best discriminates between successful and unsuccessful attempts at weaning . The measurement should be obtained during spontaneous breathing because measurements of f/VT in the presence of pressure support or CPAP will result in inaccurate predictions of weaning outcome .
The initial evaluation of f/VT was reported in 1991 . Since then, this test has been evaluated in more than 25 studies. Sensitivity ranges from 0.35 to 1 . Specificity ranges from 0 to 0.89 . At first glance, this wide scatter suggests that f/VT is an unreliable predictor of weaning outcome. This was also the viewpoint of an Evidence-Based Medicine Task Force that undertook a meta-analysis of the studies [12,13]. The Task Force, however, failed to take account of test-referral bias and spectrum bias [2,5]. When data from the studies (included in the meta-analysis) were compared with the test characteristics in the original 1991 report, taking into account Bayesian pretest probability, the weighted Pearson correlation coefficient was 0.86 (P < 0.0001) for positive-predictive value and 0.82 (P < 0.0001) for negative-predictive value (Figs. 102.3 and 102.4) . The average sensitivity in all of the studies on f/VT was 0.89, and 85% of the studies reveal sensitivities higher than 0.90 . This sensitivity compares well with commonly used diagnostic tests .
Diagnostic screening requires a simple test performed at a time when pre-test probability is low (less than 50%) . A screening test should be cheap, easy to perform, pose minimal risk to patients, and provide a quick answer. A spontaneous breathing trial that involves 30–120 minutes of monitored performance is the antithesis of a screening test.
Techniques of weaning
When a screening test is positive, the clinician proceeds to a confirmatory test . The goal of a positive result on a confirmatory test is to rule in a condition, i.e. the likelihood of a patient tolerating a trial of extubation is high. An ideal confirmatory test has a low rate of false-positive results (i.e. a high specificity) . Unfortunately, the specificity of a spontaneous breathing trial is not known. Indeed, its specificity will never be known because its determination would require an unethical experiment—extubating all patients who fail a weaning trial and counting how many require reintubation .
During a T-tube trial, the patient is completely disconnected from the ventilator and required to breathe spontaneously, while receiving an enriched supply of oxygen through a T-tube circuit. If the trial is successful, the patient is extubated. If the trial is unsuccessful, the patient is typically given at least 24 hours of respiratory muscle rest with full ventilator support before another T-tube trial is performed .
Intermittent mandatory ventilation
Intermittent mandatory ventilation (IMV) was the most popular method of weaning for many years . With IMV, the mandatory rate from the ventilator is reduced in steps of 1–3 breaths per minute, and an arterial blood gas is obtained about 30 minutes after each rate change. Titrating the number of ventilator-supported breaths in accordance with the results of arterial blood gases provides no information regarding a patient’s work of breathing (which may be excessive) .
When pressure support is used for weaning, the level of pressure is reduced gradually (decrements of 3–6 cm H2O) and titrated on the basis of the patient’s respiratory frequency . When the patient tolerates a minimal level of pressure support, he or she is extubated. What exactly constitutes a ‘minimal level of pressure support’ has never been defined .
Comparison of weaning methods
Two RCTs revealed weaning time was three times longer with IMV than with the use of T-tube trials [3,4]. In a study involving patients with respiratory difficulties on attempted weaning, T-tube trials halved the weaning time compared with pressure support . In another study, the weaning time was similar with the two methods . Performing trials of spontaneous breathing once a day is as effective as performing such trials several times a day, but much simpler . In patients not expecting to pose any particular difficulty with weaning, a half-hour trial of spontaneous breathing is as effective as a 2-hour trial . In a recent study of patients requiring prolonged mechanical ventilation, the rate of successful weaning was more than 40% higher with trials involving unassisted breathing through a tracheostomy than with pressure support .
Weaning by protocol versus usual care
Six RCTs compared the use of protocols with usual care in the management of weaning . Three found protocolized weaning was without benefit. Data from two of the other studies, although sometimes viewed as evidence of the benefit of protocolized weaning, contain internal validity problems of such magnitude that the data cannot be accepted as supportive. This leaves only one of the six studies supportive of the use of protocols .
In a RCT to determine whether the inclusion of f/Vt in a weaning protocol influenced weaning time Tanios et al.  found weaning duration was longer in the f/Vt protocol group than in the non-protocol group. In this study, patients who had a f/Vt of 105 or less progressed to a weaning trial, whereas patients with a f/Vt of 106 or higher were returned to the ventilator. When conducting research, this is exactly how a protocol must be specified and followed. No flexibility is permitted. However, it is not clinically realistic to slavishly comply with a protocol that decides an entire day of ventilator management on a one-unit difference in a single measurement of f/Vt. Rather, customizing knowledge of each patient outperforms the inflexible application of a protocol.
Decisions about weaning and decisions about extubation are commonly combined . When a patient tolerates a weaning trial without distress, a clinician feels reasonably confident that the patient will be able to sustain spontaneous ventilation after extubation. Before removing the endotracheal tube, however, the clinician must also judge whether or not the patient will be able to maintain a patent upper airway after extubation.
Of patients who are expected to tolerate extubation without difficulty, approximately 10–20% fail and require reintubation [3,4]. Mortality among patients who require re-intubation is more than six times higher than patients who can tolerate extubation . The reason for the higher mortality is unknown. It might be related to the development of new problems after extubation or to complications associated with reinsertion of a new tube. A more likely explanation is that the need for re-intubation reflects greater severity of the underlying illness .
Many find it convenient to extubate a patient once he or she can breathe comfortably on a pressure support of about 7 cmH2O and PEEP 5 cmH2O based on the belief that such ‘minimal ventilator settings’ are simply overcoming the resistance engendered by an endotracheal tube . This ignores the inflammation and oedema that develops in the upper airways after an endotracheal tube has been in place for a day or more. On removal of the tube, the mucosal swelling produces an increase in upper airway resistance. Straus et al.  demonstrated the respiratory work dissipated against the supraglottic airway after extubation is almost identical to the work dissipated against an endotracheal tube before extubation. Thus, applying any level of pressure support causes underestimation of the respiratory resistance a patient will encounter after extubation. The addition of a small amount of pressure support produces surprisingly large reductions in inspiratory work in ventilated patients: 5 cmH2O decreases inspiratory work by 31–38% and 10 cmH2O decreases work by 46–60% . Independently, addition of 5 cmH2O of PEEP can decrease work of breathing by as much as 40% in ventilated patients . In the case of a patient who might experience cardiorespiratory difficulties after extubation, it is sensible to ensure that the patient is able to breathe comfortably for about 30 minutes in the complete absence of pressure support or PEEP before removal of the endotracheal tube.
In conclusion, to minimize the likelihood of either delayed weaning or premature extubation, a two-step diagnostic strategy is recommended—measurement of weaning predictors followed by a weaning trial. Because each step constitutes a diagnostic test, clinicians must be mindful of the scientific principles of diagnostic testing when interpreting the information generated by each step. The critical step is to contemplate the possibility that a patient just might be able to tolerate weaning. Such diagnostic triggering is assisted through use of a screening test, which is the rationale for measurement of weaning-predictor tests. Importantly, one should not postpone this first step by waiting for a more complex diagnostic test, such as a T-tube trial. Because of the many complex facets of pulmonary pathophysiology that impinge on ventilator disconnection, weaning requires individualized care at a high level of sophistication.
1. Tobin MJ. (2001). Advances in mechanical ventilation. New England Journal of Medicine, 344, 1986–96.Find this resource:
2. Tobin MJ and Jubran A (2012). Weaning from mechanical ventilation. In Tobin MJ. (ed.) Principles and Practice of Mechanical Ventilation, 3rd edn, pp. 1185–220. New York, NY: McGraw-Hill, Inc.Find this resource:
3. Brochard L, Rauss A, Benito S, et al. (1994). Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. American Journal of Respiratory and Critical Care Medicine, 150, 896–903.Find this resource:
4. Esteban A, Frutos F, Tobin MJ, et al. (1995). A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group. New England Journal of Medicine, 332, 345–50.Find this resource:
5. Feinstein AR (1985). Clinical Epidemiology: The Architecture of Clinical Research. Philadelphia, PA: Saunders.Find this resource:
6. Tobin MJ and Jubran A. (2006). Variable performance of weaning-predictor tests: Role of Bayes’ theorem and spectrum and test-referral bias. Intensive Care Medicine, 32, 2002–12.Find this resource:
7. Casscells W, Schoenberger A, and Graboys TB. (1978). Interpretation by physicians of clinical laboratory results. New England Journal of Medicine, 299, 999–1001.Find this resource:
8. Laghi F, Cattapan SE, Jubran A, et al. (2003). Is weaning failure caused by low-frequency fatigue of the diaphragm? American Journal of Respiratory and Critical Care Medicine, 167, 120–7.Find this resource:
9. Tobin MJ, Laghi F, and Jubran A. (2012). Ventilatory failure, ventilator support, and ventilator weaning. Comprehensive Physiology, 2, 1–51.Find this resource:
10. Tobin MJ, Perez W, Guenther SM, et al. (1986). The pattern of breathing during successful and unsuccessful trials of weaning from mechanical ventilation. American Reviews of Respiratory Disease, 134, 1111–18.Find this resource:
11. Yang KL and Tobin MJ. (1991). A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. New England Journal of Medicine, 324, 1445–50.Find this resource:
12. MacIntyre NR, Cook DJ, Ely EW Jr, et al. (2001). 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, 120(Suppl. 6), 375S–95S.Find this resource:
13. Meade M, Guyatt G, Cook D, et al. (2001). Predicting success in weaning from mechanical ventilation. Chest, 120, 400S–24S.Find this resource:
14. Sassoon CS (2012). Intermittent mechanical ventilation. In: Tobin MJ (ed.) Principles and Practice of Mechanical Ventilation, 3rd edn, pp. 17–98. New York, NY: McGraw-Hill.Find this resource:
15. Esteban A, Alia I, Tobin MJ, et al. (1999). Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group. American Journal of Respiratory and Critical Care Medicine, 159, 512–18.Find this resource:
16. Jubran A, Grant BJB, Duffner LA, et al. (2013). Weaning from prolonged mechanical ventilation. Effect of pressure support vs unassisted breathing through a tracheostomy collar on weaning duration in patients requiring prolonged mechanical ventilation: a randomized trial. Journal of the American Medical Association, 309, 671–7.Find this resource:
17. Tanios MA, Nevins ML, Hendra KP, et al. (2006). A randomized, controlled trial of the role of weaning predictors in clinical decision making. Critical Care Medicine, 34(10), 2530–5.Find this resource:
18. Tobin MJ and Laghi F. (2012). Extubation. In: Tobin MJ (ed.) Principles and Practice of Mechanical Ventilation, 3rd edn, pp. 1221–36. New |York, NY: McGraw-Hill Inc.Find this resource:
19. Tobin MJ. (2012). Extubation and the myth of ‘minimal ventilator settings’. American Journal of Respiratory and Critical Care Medicine, 185(4), 349–50.Find this resource:
20. Straus C, Louis B, Isabey D, et al. (1998). Contribution of the endotracheal tube and the upper airway to breathing workload. American Journal of Respiratory and Critical Care Medicine, 157, 23–30.Find this resource: