American Journal of Respiratory and Critical Care Medicine

Half the patients in an intensive care unit receive mechanical ventilation and almost half of intubated time is devoted to weaning. Accordingly, weaning constitutes an enormous workload for intensive care staff (1).

Two deliberate steps are involved in weaning. First, patient readiness is tested with physiological measurements, usually called weaning predictors (2, 3). Second, the patient is evaluated while ventilator support is decreased, gradually or abruptly (4, 5). This two-step approach has been found more dependable than allowing physicians wean in a desultory fashion (6).

But findings reported in this issue of the Journal (pp. 673–678) appear to turn accepted wisdom on its head.

In a prospective controlled trial, Krishnan and coworkers (7) compared protocolized weaning with usual care. Patients assigned to protocolized weaning were screened in the morning by a respiratory therapist and stable patients had frequency-to-tidal volume ratio measured. If the ratio was 105 or less, respiratory and nursing staff undertook a spontaneous breathing trial (without physician intervention). If the patient passed the one-hour trial, the physician was informed. Patients failing the assessment were rested until the following day. In the usual care arm, patients were managed at the discretion of their physicians. Patients did not undergo any scheduled screening, although physicians were free to make measurements at the bedside.

Clinical outcomes did not differ between the two groups. Duration of mechanical ventilation, the primary outcome, was equivalent for protocolized weaning and usual care (60.4 versus 68.0 hours), as was the rate of successful weaning (74.7 versus 75.2%).

At first glance, the findings of Krishnan and coworkers (7) suggest that previous research on weaning has not improved clinical practice. But interpretation of information depends on context. In research, special trouble is taken to ensure relevant context by studying a comparison group. Yet data from control groups have served mainly as backdrop, and the spotlight has been shone mostly on the treated group. Today, however, selection of control groups is moving more and more to center stage (8). It is no longer acceptable to compare a new bronchodilator agent against placebo (instead, the new agent must be compared against the best preexisting treatment) (8). Likewise, interpretation of research findings with a new ventilator strategy depends on how the control group is ventilated (9).

Close examination of the control group of Krishnan and coworkers (7) tells us what questions we can and cannot answer with the new data. Do patients weaned according to the usual practice of Hopkins physicians do as well as patients subjected to protocolized weaning? Yes. Do the data indicate that the two-step approach to weaning (testing patient readiness followed by evaluation of the patient as ventilator assistance is deliberately decreased) is unhelpful? No—because that question was not tested. And it is doubtful whether the question could have been satisfactorily tested. To do so, the investigators would have had to compare their 2000–2001 usual care group with matched patients weaned in their unit before the late 1980s—before the emergence of physiological principles used when weaning a patient today (25, 10).

Quantification of usual care is a subject of increasing interest to intensivists (8, 11, 12). It is not easy to capture it in a manner that enables meaningful comparison with a new management strategy. Usual care also changes constantly—as every malpractice attorney knows. To see how care of the weaning patient has changed over time, I opened a text from my fellowship years. Discussing weaning prediction and readiness for extubation, the author writes: “When the patient can breathe unassisted around the clock, and is moving a reasonable amount of air without undue effort, and can walk for short distances consistent with his general physical condition, and when ventilation is satisfactory and stable by blood gas values, it is time to consider removal of the endotracheal tube” (13). Today, we know that most patients can be extubated after a spontaneous breathing trial lasting only a half hour (14).

What other lessons can we learn from the new data? One, the study shows that it's possible to include usual care as a control group when doing research on ventilator protocols in an intensive care unit—the second such study by Krishnan and collaborators. These investigators previously reported the outcome of patients with the acute respiratory distress syndrome ventilated according to usual practice (from their study of patients refusing to participate in the ARDS Network trial) (15).

Two, we need to make a distinction between the use of algorithms in research protocols and their subsequent application in everyday practice. When formulating a research algorithm, each step must be specified with exacting precision (16). In the trial of Krishnan and coworkers, patients who had a frequency-to-tidal volume ratio of 104 or less progressed to a spontaneous breathing trial whereas patients with a ratio of 105 or higher were returned to the ventilator (for another day). And this is exactly how a protocol for a controlled trial must be specified and followed (16). No flexibility. No weasel words. But a competent clinician would think it daft to slavishly comply with a protocol that decided an entire day of ventilator management on a one-unit difference in a single measurement of frequency-to-tidal volume ratio. An intelligent physician who customizes knowledge generated by a previous research protocol to the particulars of each patient is expected to outperform the inflexible application of that protocol—as reflected by the longer time between initiation of a spontaneous breathing trial and extubation in the protocolized versus usual care group: 3.0 versus 1.6 hours. It is not the inflexibility of an algorithm that we want when caring for patients, but the new physiological principles that arise from successful testing of the algorithm.

In the study of Krishnan and coworkers, the question is not what went wrong with protocolized weaning but what was right with usual care. Physicians are adept at extracting principles that emerge from research studies and incorporating them into their everyday practice. Once these principles have crept into a clinician's brain, they cannot be extirpated surgically. To interpret the study as saying it's not necessary to undertake weaning in a deliberate manner would be to throw a physiological baby out with the protocolized bath water.

1. Tobin MJ. Advances in mechanical ventilation. N Engl J Med 2001;344:1986–1996.
2. Tobin MJ, Perez W, Guenther SM, Semmes BJ, Mador MJ, Allen SJ, Lodato RF, Dantzker DR. The pattern of breathing during successful and unsuccessful trials of weaning from mechanical ventilation. Am Rev Respir Dis 1986;134:1111–1118.
3. Yang K, 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.
4. Brochard L, Rauss A, Benito S, Conti G, Mancebo J, Rekik N, Gasparetto A, Lemaire F. Comparison of three methods of gradual withdrawing from ventilatory support during weaning from mechanical ventilation. Am J Respir Crit Care Med 1994;150:896–903.
5. Esteban A, Frutos F, Tobin MJ, et al. A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med 1995;332:345–350.
6. Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder WW, Bowton DL, Haponik EF. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996;335:1864–1869.
7. Krishnan JA, Moore D, Robeson C, Rand CS, Fessler HE. A prospective, controlled trial of a protocol-based strategy to discontinue mechanical ventilation. Am J Respir Crit Care Med 2004;169:673–678.
8. Miller FG, Silverman HJ. The ethical relevance of the standard of care in the design of clinical trials. Am J Respir Crit Care Med 2004;169:562–564.
9. Eichacker PQ, Gerstenberger EP, Banks SM, Cui X, Natanson C. Metaanalysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med 2002;166:1510–1514.
10. Marini JJ, Smith TC, Lamb VJ. External work output and force generation during synchronized intermittent mandatory ventilation: effect of machine assistance on breathing effort. Am Rev Respir Dis 1988;138:1169–1179.
11. Parshuram C, Kavanagh B. Meta-analysis of tidal volumes in ARDS. Am J Respir Crit Care Med 2003;167:798.
12. Brower RG, Rubenfeld G, Thompson BT. Meta-analysis of tidal volumes in ARDS. Am J Respir Crit Care Med 2003;168:255–256.
13. Egan DF. Fundamentals of respiratory therapy, 3rd edition. St Louis: CV Mosby; 1977.
14. Esteban A, Alía I, Tobin MJ, Gil A, Gordo F, Vallverdú I, Blanch L, Bonet A, Vázquez A, de Pablo R, et al. Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Am J Respir Crit Care Med 1999;159:512–518.
15. Krishnan JA, Hayden D, Schoenfeld D, Bernard G, Brower R, for the NHLBI ARDSNetwork Investigators. Outcome of participants vs. eligible nonparticipants in a clinical trial of critically ill patients. Am J Respir Crit Care Med 2000;161:A210.
16. Morris AH. Algorithm-based decision making. In: Tobin MJ, editor. Principles and practice of intensive care monitoring. McGraw-Hill, Inc: New York; 1998. p. 1355–1381.

Related

No related items
American Journal of Respiratory and Critical Care Medicine
169
6

Click to see any corrections or updates and to confirm this is the authentic version of record