Following Protocol
Weaning Difficult-to-Wean Patients with Chronic Obstructive Pulmonary Disease

Nicholas S. Hill, M.D.

Brown University, Providence, Rhode Island

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Difficult-to-wean patients, that is, those who fail to wean after repeated attempts beyond 14 to 21 d, consume a disproportionate share of health care resources including hospital beds, personnel time, and money. In addition, these patients are at much higher risk than those who wean earlier for morbidity and mortality, with some studies showing survival rates to hospital discharge as low as 25% (1). Techniques and strategies that enhance the weaning process in such patients are sorely needed.

In this issue of AJRCCM (pp. 225-230), Vitacca and coworkers (2) address two main questions regarding difficult-to-wean patients with chronic obstructive pulmonary disease (COPD). First, which is the more efficient weaning technique, pressure support ventilation or repeated spontaneous breathing (T-piece) trials? And second, does the institution of a standardized weaning protocol facilitate weaning compared with standard physician-directed weaning? To answer the first question, the authors performed a prospective randomized trial in three long-term weaning units in northern Italy. Among 114 referred patients, 39 were excluded because of a non-COPD diagnosis or cancer, and 23 (31%) passed an initial 48-hour T-piece trial and were extubated.

The remaining 52 patients were randomized to receive twice daily T-piece trials or pressure support ventilation with twice daily 2-cm H₂O decrements in inspiratory pressure as tolerated. The authors found that weaning success rates were virtually identical between the groups (73 versus 77%), and mortality rates (11.5 versus 7.6%) and lengths of stay in the weaning unit and hospital did not differ significantly. They conclude that spontaneous breathing trials and pressure support ventilation are equally effective in weaning difficult-to-wean patients.

However, they fail to consider that the weaning time was 51 h shorter for T-piece trials than for pressure support ventilation (130 versus 181 h). Although not statistically significant, this is certainly a strong trend, amounting to a 28% advantage for T-piece trials. The authors calculated that a total of 90 patients would have been necessary to detect even a 20% difference between groups. Thus, the study was insufficiently powered to detect a difference of 28%, and the possibility that T-piece trials were actually more efficient in weaning patients cannot be rejected. It is apparent, however, that this possible advantage of T-piece weaning did not translate into trends for improvements in other outcomes, perhaps because many patients had comorbidities or rehabilitation needs that necessitated prolonged hospitalization regardless.

To answer the second question, the authors resorted to a retrospective control group from one of the weaning units in the randomized trial. This group consisted of 62 patients admitted to the same unit during the previous 2 yr and matched for age, Acute Physiology and Chronic Health Evaluation (APACHE) score, body weight, and arterial blood gases on the ventilator. The authors found that weaning rates (87 versus 70%), hours of weaning (103 versus 170 h), and lengths of stay in the weaning unit (27 versus 38 d) and hospital (38 versus 47 d) were all significantly better in the prospective protocol group than the retrospective group (all p < 0.05). The authors conclude that "application of a well-defined protocol" may result in better outcomes than uncontrolled clinical practice in difficult-to-wean patients.

Although the authors acknowledge the "limitations of an historical comparison," it is worth elucidating them here. First, it is impossible to be certain that selection criteria were identical between the groups, even though patients were well matched. Characteristics such as neurologic status, cough efficacy, or copiousness of secretions could have differed between the groups and contributed to differences in weaning success rates. In addition, even though the unit personnel remained the same throughout, their patient management skills could have improved with experience and practices relating to use of sedation or discharging patients could have changed. Thus, differences in patient selection or changes over time could explain the different outcomes between the retrospective and prospective groups. The strongest conclusion that can be drawn is that the institution of a protocol might have contributed to improved outcomes.

Nonetheless, the findings of Vitacca and coworkers are buttressed by their consistency with prior studies of shorter-term weaning after bouts of respiratory failure. No weaning technique has consistently demonstrated superiority over another (3, 4), and the institution of formalized weaning protocols has been associated with expedited weaning (5, 6). If, while acknowledging the concerns about methodology, we accept that accumulating evidence supports the contention that standard protocols expedite weaning, should we ask by what mechanism? Understanding the answer might enable refinements of future protocols that could enhance key aspects and further facilitate the weaning process.

One approach to answering the question is to consider how a protocol might facilitate repair of the basic defects that retard weaning. Studies of difficult-to-wean patients with COPD have implicated an imbalance in the load-capacity relationship as the major pathophysiologic difference from successfully weaned patients (7, 8). Weaning failures have enhanced central drive, but maximal inspiratory pressures and FEV₁ values are lower (7), and pressure-time products and levels of intrinsic positive end-expiratory pressure (PEEP) are higher compared with successfully weaned patients (8). Successful weaning can occur only if the breathing load is decreased by lowering airway resistance and intrinsic PEEP and/or the breathing capacity is increased by improving respiratory muscle strength and endurance.

Can a weaning protocol expedite the rate of recovery and re-establish the load-capacity balance more rapidly than usual practice? In difficult-to-wean patients, these changes occur slowly, if they occur at all, as a consequence of resolution of infection, reduced airway inflammation, and muscle reconditioning from nutritional repletion and rehabilitation. Yet the protocol of Vitacca and colleagues includes nothing about medical management; it merely dictates that weaning trials be performed twice daily. Can this simple mechanism facilitate the resolution of complex pathophysiologic defects more rapidly than usual practice?

It is unclear how weaning trials, whether pressure support or T-piece, can speed the resolution of inflammation or other basic pathophysiologic defects. More likely, they work by obligating medical personnel to pay closer attention to patients. By dictating daily trials, they ensure that patients who are making improvements will be weaned as soon as they are ready. Hours or even days may be saved because weaning trials are performed in a timely fashion, preventing delays caused by the assumption that the patient is still unweanable, or distraction of personnel by sicker patients. Further, by providing guidelines for initiation and termination of weaning trials, protocols help to ensure that weaning moves along at a comfortable pace for the patient, neither too slowly nor too rapidly, the latter delaying the weaning process by overtaxing the respiratory muscles and contributing to fatigue.

Despite its acknowledged weaknesses, the Vitacca study provides some helpful insights into optimal weaning approaches to difficult-to-wean patients with COPD. After transfer to a weaning unit, an early spontaneous breathing trial is useful to identify patients who are weanable despite the difficult-to-wean label. Although spontaneous breathing trials may permit slightly more rapid weaning than pressure support trials, they appear to offer little advantage over pressure support with regard to overall weaning rates, mortality, or lengths of stay. Finally, protocols that dictate daily weaning trials are likely to improve the efficiency of weaning. Further studies will be needed to confirm these findings, to determine the optimal length and frequency of spontaneous breathing trials in difficult-to-wean patients, and to ascertain what aspects of a standardized protocol are most important.

	References

TOP ARTICLE REFERENCES

1. Spicher JR, White DP. Outcome and function following prolonged mechanical ventilation. Arch Intern Med 1987; 147: 421-425 [Abstract/Free Full Text].

2. Vitacca M, Vianello A, Colombo D, Clini E, Porta R, Bianchi L, Arcaro G, Vitale G, Guffanti E, Lo Coco A, et al. Comparison of two methods for weaning COPD patients requiring mechanical ventilation for more than 15 days. Am J Respir Crit Care Med 2001;164:225-230.

3. Brochard L, Rauss A, Benito S, Conti G, Mancebo J, Rekik N, Gasparetto A, Lemaire F. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. Am J Respir Crit Care Med 1994; 150: 896-903 [Abstract].

4. Esteban A, Frutos F, Tobin JM, Alia I, Solsona JF, Valverdu I, Fernandez R, de la Cal MA, Benito S, Tomas R, et al . . A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med 1995; 332: 346-389 .

5. Saura P, Blanch L, Mestre J, Valles J, Artigas A, Fernandez R. Clinical consequences of the implementation of a weaning protocol. Intensive Care Med 1996; 22: 1052-1056 [Medline].

6. Kollef MH, Shapiro SD, Silver P, St. John RE, Prentice D, Sauer S, Ahrens TS, Shannon W, Baker-Clinkscale D. A randomized, controlled trial of protocol-directed versus physician-directed weaning from mechanical ventilation. Crit Care Med 1997; 25: 567-574 [Medline].

7. Purro A, Appendini L, De Gaetano A, Gudjonsdottir M, Donner CF, Rossi A. Physiologic determinants of ventilator dependence in long-term mechanically ventilated patients. Am J Respir Crit Care Med 2000; 161: 1115-1123 [Abstract/Free Full Text].

8. Jubran A, Tobin MJ. Pathophysiologic basis of acute respiratory distress in patients who fail a trial of weaning from mechanical ventilation. Am J Respir Crit Care Med 1997; 155: 906-915 [Abstract].